Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов

Приведен обзор и анализ возможностей применения технологии CUDA для ускорения расчетов в области структурной биологии и биоинформатики. На примере работы с программой HEX 6.1 выполнен сравнительный анализ прироста производительности и качества результатов жесткого докинга низкомолекулярных соединени...

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Бібліографічні деталі
Опубліковано в: :Цитология и генетика
Дата:2012
Автори: Демчук, О.Н., Карпов, П.А., Блюм, Я.Б.
Формат: Стаття
Мова:Російська
Опубліковано: Інститут клітинної біології та генетичної інженерії НАН України 2012
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Онлайн доступ:https://nasplib.isofts.kiev.ua/handle/123456789/126471
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Назва журналу:Digital Library of Periodicals of National Academy of Sciences of Ukraine
Цитувати:Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов / О.Н. Демчук, П.А. Карпов, Я.Б. Блюм // Цитология и генетика. — 2012. — Т. 46, № 3. — С. 55-64. — Бібліогр.: 54 назв. — рос.

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Digital Library of Periodicals of National Academy of Sciences of Ukraine
_version_ 1860246651869855744
author Демчук, О.Н.
Карпов, П.А.
Блюм, Я.Б.
author_facet Демчук, О.Н.
Карпов, П.А.
Блюм, Я.Б.
citation_txt Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов / О.Н. Демчук, П.А. Карпов, Я.Б. Блюм // Цитология и генетика. — 2012. — Т. 46, № 3. — С. 55-64. — Бібліогр.: 54 назв. — рос.
collection DSpace DC
container_title Цитология и генетика
description Приведен обзор и анализ возможностей применения технологии CUDA для ускорения расчетов в области структурной биологии и биоинформатики. На примере работы с программой HEX 6.1 выполнен сравнительный анализ прироста производительности и качества результатов жесткого докинга низкомолекулярных соединений различных классов на поверхности FtsZ белка из Arabidopsis thaliana. Идентифицировано несколько потенциальных сайтов связывания бензимидазолов с растительным FtsZ. Наводиться огляд та аналіз можливостей застосування технології CUDA для прискорення обчислень в галузі структурної біології та біоінформатики. На прикладі роботи з програмою Hex 6.1 здійснено порівняльний аналіз приросту продуктивності та якості результатів жорсткого докінгу низькомолекулярних сполук різних класів на поверхні FtsZ-білка із Arabidopsis thaliana. Ідентифіковано декілька потенційних сайтів зв’язування бензімідазолів із рослинним FtsZ. The opportunities to apply the CUDA technology for faster computations in structural biology and bioinformatics are reviewed and analyzed. Using HEX 6.1 software, we performed a comparative analysis of the efficiency and the increase in quality after CUDA application. The work was conducted on the example of rigid docking of low-molecular-weight compounds of different classes on the surface of the Arabidopsis thaliana FtsZ. Several potential binding sites of benzimidazoles to the plant FtsZ were identified.
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fulltext 55ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2012. ¹ 3 УДК 577.112.7(577.332+004.42) О.Н. ДЕМЧУК, П.А. КАРПОВ, Я.Б. БЛЮМ Институт пищевой биотехнологии и геномики НАН Украины, Киев E-mail: demom79@gmail.com ДОКИНГ НИЗКОМОЛЕКУЛЯРНЫХ ЛИГАНДОВ НА МОЛЕКУЛЕ РАСТИТЕЛЬНОГО FtsZ-БЕЛКА: ПРИМЕНЕНИЕ ТЕХНОЛОГИИ CUDA ДЛЯ УСКОРЕНИЯ РАСЧЕТОВ Ïðèâåäåí îáçîð è àíàëèç âîçìîæíîñòåé ïðèìå- íåíèÿ òåõíîëîãèè CUDA äëÿ óñêîðåíèÿ ðàñ÷åòîâ â îáëàñòè ñòðóêòóðíîé áèîëîãèè è áèîèíôîðìàòèêè. Íà ïðèìåðå ðàáîòû ñ ïðîãðàììîé Hex 6.1 âûïîëíåí ñðàâíèòåëüíûé àíàëèç ïðèðîñòà ïðîèçâîäèòåëüíîñ- òè è êà÷åñòâà ðåçóëüòàòîâ æåñòêîãî äîêèíãà íèçêî- ìîëåêóëÿðíûõ ñîåäèíåíèé ðàçëè÷íûõ êëàññîâ íà ïî- âåðõíîñòè FtsZ áåëêà èç Arabidopsis thaliana. Èäåí- òèôèöèðîâàíî íåñêîëüêî ïîòåíöèàëüíûõ ñàéòîâ ñâÿ- çûâàíèÿ áåíçèìèäàçîëîâ ñ ðàñòèòåëüíûì FtsZ. Ââåäåíèå. Ìîäåëèðîâàíèå ìåæìîëåêóëÿð- íûõ âçàèìîäåéñòâèé ÿâëÿåòñÿ îäíîé èç íàè- áîëåå âîñòðåáîâàííûõ âû÷èñëèòåëüíûõ çàäà÷ ñòðóêòóðíîé áèîèíôîðìàòèêè [1]. Òðàäèöèîí- íî äëÿ ðàñ÷åòîâ òàêîãî òèïà ðåñóðñîçàòðàòíûõ çàäà÷ in silico ïðèìåíÿþòñÿ âû÷èñëèòåëüíûå ïëàòôîðìû, îñíîâàííûå íà èñïîëüçîâàíèè êàê îäèíî÷íûõ CPU (Central Processing Unit), òàê è ìíîãîïðîöåññîðíîé âû÷èñëèòåëüíîé ñðå- äû (êëàñòåðíûå ðåøåíèÿ, ãðèä) [2, 3]. Ñðàâíè- òåëüíî íåäàâíî, áëàãîäàðÿ ïîÿâëåíèþ òåõíî- ëîãèé ðàñ÷åòîâ ñ èñïîëüçîâàíèåì ãðàôè÷åñêèõ ïðîöåññîðîâ (GPU – Graphics Processing Unit) [4] è, â ÷àñòíîñòè, òåõíîëîãèè CUDA (Com- pute Unified Device Architecture), GPU âû÷èñ- ëåíèÿ ñòàëè ïðèìåíÿòüñÿ äëÿ ðåøåíèÿ øè- ðîêîãî ñïåêòðà íàó÷íûõ çàäà÷ [3], â òîì ÷èñ- ëå äëÿ âûïîëíåíèÿ áèîèíôîðìàöèîííûõ è ìîëåêóëÿðíî-áèîëîãè÷åñêèõ ðàñ÷åòîâ [5].Ýòî ïîëîæèòåëüíî ñêàçàëîñü íà ñêîðîñòè ðåàëè- çàöèè îòäåëüíûõ âû÷èñëèòåëüíûõ îïåðàöèé è ïðèâåëî ê çíà÷èòåëüíîìó ñîêðàùåíèþ ðàñ- ÷åòíîãî âðåìåíè, íåîáõîäèìîãî äëÿ âûïîëíåíèÿ ðÿäà àëãîðèòìîâ è áèîèíôîðìàöèîííûõ èñ- ñëåäîâàíèé â öåëîì. Òàê, ïðèìåíåíèå GPU äëÿ âûðàâíèâàíèÿ ïîñëåäîâàòåëüíîñòåé ÄÍÊ è áåëêîâ ñîêðà- ùàåò âðåìÿ ðàñ÷åòîâ ñ 10 [6, 7] äî 100 ðàç [8] ïî ñðàâíåíèþ ñ ðàñ÷åòàìè, âûïîëíåííûìè ïðè èñïîëüçîâàíèè öåíòðàëüíîãî ïðîöåññîðà (CPU). Ïîêàçàíî, ÷òî ïðèìåíåíèå GPU ïî- çâîëÿåò ñîêðàòèòü âðåìÿ, íåîáõîäèìîå äëÿ âûïîëíåíèÿ ðàñ÷åòîâ ìîëåêóëÿðíîé äèíàìè- êè â 10–100 ðàç [9, 10], êâàíòîâîé õèìèè äî 130 ðàç [11], à âåéâëåò-àíàëèçà ìàññ-ñïåêòðî- ãðàôè÷åñêèõ äàííûõ – áîëåå ÷åì â 200 ðàç [12]. Ïðèìåíåíèå GPU äëÿ ðàñ÷åòà äîñòóïíîé ïîâåðõíîñòè áåëêà â 100–300 ðàç ñîêðàùàåò âðåìÿ âû÷èñëåíèé â çàâèñèìîñòè îò ðàçìå- ðîâ ìîäåëèðóåìîé ñèñòåìû [13]. Íåóäèâèòåëüíî, ÷òî êîëè÷åñòâî ïðèêëàä- íûõ ïðîãðàìì, ïîääåðæèâàþùèõ âîçìîæ- íîñòü ìîëåêóëÿðíûõ ðàñ÷åòîâ ñ ïðèìåíåíèåì GPU, ñòðåìèòåëüíî âîçðàñòàåò [14]. Áåçóñëîâ- íûì ëèäåðîì â îáëàñòè ðàçâèòèÿ òåõíîëîãèè GPU âû÷èñëåíèé â íàñòîÿùåå âðåìÿ ÿâëÿåòñÿ ôèðìà nVidia è ðàçðàáîòàííàÿ ýòîé êîìïàíèåé òåõíîëîãèÿ CUDA [15]. Ïðàêòè÷åñêè ïîëíûé ñïèñîê ïðèëîæåíèé, ïîääåðæèâàþùèõ òåõíî- ëîãèþ CUDA, ïðåäñòàâëåí íà ñòðàíèöå «CUDA Zone» îôèöèàëüíîãî web-ñàéòà êîìïàíèè nVidia (http://www.nvidia.ru/).  íàñòîÿùåå âðå-© Î.Í. ÄÅÌ×ÓÊ, Ï.À. ÊÀÐÏÎÂ, ß.Á. ÁËÞÌ, 2012 56 ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2012. ¹ 3 Î.Í. Äåì÷óê, Ï.À. Êàðïîâ, ß.Á. Áëþì ìÿ ñïèñîê íàñ÷èòûâàåò áîëåå 20 ïðîãðàìì, ïðåäíàçíà÷åííûõ äëÿ ðåøåíèÿ çàäà÷ áèîèí- ôîðìàòèêè è ñòðóêòóðíîé áèîëîãèè. Òàê, äëÿ îäíîãî èç íàèáîëåå âîñòðåáîâàííûõ â áèîèíôîðìàòèêå èíñòðóìåíòîâ – BLAST (The Basic Local Alignment Search Tool, NCBI- BLAST www.ncbi.nlm.nih.gov) ïðåäñòàâëåíû ðåøåíèÿ ñ ïîääåðæêîé òåõíîëîãèè CUDA: GPU-BLAST (http://eudoxus.cheme.cmu.edu/ gpublast/), ðàáîòàþùèé â ÷åòûðå ðàçà áûñòðåå ïðè èäåíòè÷íîñòè ðåçóëüòàòîâ ïîèñêà òðàäè- öèîííîìó BLASTn [16], è CUDA-BLASTP [17], ïðåäíàçíà÷åííûé äëÿ ñêàíèðîâàíèÿ áîëüøèõ ìàññèâîâ àìèíîêèñëîòíûõ ïîñëåäî- âàòåëüíîñòåé. Êðîìå òîãî, â ñîñòàâ óïîìÿ- íóòûõ ðåøåíèé âõîäèò ïîäïðîãðàììà äëÿ êîíâåðòàöèè ïîñëåäîâàòåëüíîñòåé â ôîðìàò, êîòîðûé îïòèìèçèðîâàí äëÿ èñïîëüçîâàíèÿ â ïðèëîæåíèÿõ BLAST, àäàïòèðîâàííûõ äëÿ CUDA (http://www.nvidia.com/object/blastp_on_ tesla.html) [17]. Äðóãàÿ ïðîãðàììà, CUDASW++ (http://cu- dasw.sourceforge.net/), ïðåäíàçíà÷åíà äëÿ ïî- èñêà â áàçàõ äàííûõ àìèíîêèñëîòíûõ ïî- ñëåäîâàòåëüíîñòåé ñ ïðèìåíåíèåì àëãîðèòìà Ñìèòà-Âàòåðìàíà [18, 19]. Óñòàíîâëåíî, ÷òî ïðè èñïîëüçîâàíèè ãðàôè÷åñêèõ óñêîðèòåëåé NVIDIA GeForce (GTX 280 è GTX 295) âðåìÿ ïîèñêà ñ ïîìîùüþ ïðîãðàììû CUDASW++ ñîêðàùàåòñÿ â 10–50 ðàç ïî ñðàâíåíèþ ñ NCBI-BLAST [18]. Äëÿ òàêîé çàäà÷è, êàê ïîèñê êîíñåðâàòèâ- íûõ ìîòèâîâ ïîñëåäîâàòåëüíîñòåé, íà îñíîâå ïàêåòà MEME (V. 3.5.4) [20] ñîçäàíà âåðñèÿ äëÿ CUDA – CUDA-MEME (mCUDA- MEME) (http://www.nvidia.com/object/meme_ on_tesla.html) [21, 17]. Äëÿ îïòèìèçàöèè ðàñ÷åòîâ ñ èñïîëüçîâà- íèåì ñêðûòûõ ìîäåëåé Ìàðêîâà (ÍÌÌ) ðàñ- ïàðàëëåëèâàíèå íà GPU ðåàëèçîâàíî â ïðî- ãðàììå GPU-HMMER (http://www.mpihmmer. org/) (http://www.nvidia.com/object/hmmer_on_ tesla.html), ñêîðîñòü ðàáîòû êîòîðîé â 60–100 ðàç âûøå, ÷åì ó HMMER v.3.0 [22, 23]. Îäíàêî íàèáîëåå âîñòðåáîâàííîé òåõíî- ëîãèÿ CUDA ÿâëÿåòñÿ â îáëàñòè ñòðóêòóð- íîé áèîèíôîðìàòèêè [25], ãäå ñîñðåäîòî÷åíî íàèáîëüøåå êîëè÷åñòâî ïðîãðàìì (NAMD 2.7 beta, VMD 1.8.7, Amber Alpha patch, HOOMD 0.8.1, Autodock 0.9, CHARMM Beta, GROMACS 4.0, LAMMPS Alpha è äð.), ïðåäíàçíà÷åííûõ äëÿ ðåøåíèÿ ñòðóêòóðíûõ ìîëåêóëÿðíî-áèîëîãè÷åñêèõ çàäà÷, òàêèõ êàê ìîëåêóëÿðíîå ìîäåëèðîâàíèå, ìîëåêóëÿðíûé äîêèíã, ñèìóëÿöèÿ ìîëåêóëÿðíîé äèíàìèêè è ò.ä. [27–30].  2007 ã. ãðóïïà èññëåäîâàòå- ëåé èç óíèâåðñèòåòà Èëëèíîéñà â Óðáàíà- Øàìïåéí (UIUC – «Biophysics Groupe») âû- ïóñòèëà ïîïóëÿðíûé ïðîãðàììíûé ïàêåò äëÿ ðàñ÷åòîâ ìîëåêóëÿðíîé äèíàìèêè NAMD ñ ïîääåðæêîé òåõíîëîãèè CUDA (http://www. ks.uiuc.edu/Research/gpu/) [31]. Ïðè îñóùå- ñòâëåíèè ðàñ÷åòîâ ñ èñïîëüçîâàíèåì ïàêåòà NAMD è ðåñóðñà NCSA ÷åòûðå ãðàôè÷åñêèõ óñêîðèòåëÿ Tesla (http://www.nvidia.com/) ïðåâ- çîøëè ïî âû÷èñëèòåëüíîé ìîùíîñòè êëàñòåð èç 16 ÷åòûðåõúÿäåðíûõ CPU (http://www.ncsa. illinois.edu/UserInfo/Resources/Hardware/Inte l64TeslaCluster/).  íàñòîÿùåå âðåìÿ ðåàëèçîâàíà èíòåãðà- öèÿ NAMD ñ ïîïóëÿðíîé ïðîãðàììîé VMD («Biophysics Groupe» – www.ks.uiuc.edu/Re- search/vmd/), ÷òî ïðè èñïîëüçîâàíèè CUDA ïîçâîëÿåò îñóùåñòâëÿòü àíàëèç, 3D-âèçóàë- çàöèþ è àíèìàöèþ áîëüøèõ ìîëåêóëÿðíûõ ñèñòåì. VMD (Visual Molecular Dynamics) òàêæå èìååò ïîääåðæêó CUDA ñ ðàñïàðàë- ëåëèâàíèåì íà GPU îò nVidia. «Biophysics Groupe» óäàëîñü èíòåãðèðîâàòü òåõíîëîãèþ CUDA â ïðèëîæåíèÿ äëÿ ñèìóëÿöèè ìîëå- êóëÿðíîé äèíàìèêè [32], îòîáðàæåíèÿ ìîëå- êóëÿðíûõ îðáèòàëåé [26, 33], ðàñ÷åòû ïîçè- öèðîâàíèÿ èîíîâ [9], ñèìóëÿöèþ êóëîíîâ- ñêèõ âçàèìîäåéñòâèé [5] è îáðàáîòêó äàííûõ ìèêðîñêîïèè [34]. Ýòî ïîçâîëèëî óâåëè÷èòü ñêîðîñòü ðàáîòû ñîîòâåòñòâóþùèõ ïðèëîæå- íèé îò 20 äî 100 ðàç (http://www.ks.uiuc.edu/ Research/gpu/). Íåäàâíî áûëà ðàçðàáîòàíà CUDA-âåðñèÿ ïàêåòà ñèëîâûõ ïîëåé AMBER (http://ambermd. org/gpus/). Ïðèìåíåíèå GPU Tesla ïðè ìîäå- ëèðîâàíèè ìîëåêóëÿðíîé äèíàìèêè â ïîëå Amber äëÿ ñèñòåì ñ èñïîëüçîâàíèåì ÿâíîãî è íåÿâíîãî ðàñòâîðèòåëÿ ðàñ÷åòíîå âðåìÿ ñî- êðàùàëîñü áîëåå ÷åì â 10 ðàç ïî ñðàâíåíèþ ñ ñåðâåðîì íà îñíîâå ÷åòûðåõúÿäåðíîãî CPU [35]. Ïàêåò ñèëîâûõ ïîëåé Gromacs (http://www. gromacs.org/) ðàçðàáîòàí äëÿ ìîäåëèðîâàíèÿ äèíàìèêè è ìèíèìèçàöèè ýíåðãèè áåëêîâ, íó- êëåèíîâûõ êèñëîò è ëèïèäîâ, à òàêæå ïðåä- 57ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2012. ¹ 3 Äîêèíã íèçêîìîëåêóëÿðíûõ ëèãàíäîâ íà ìîëåêóëå ðàñòèòåëüíîãî FtsZ-áåëêà íàçíà÷åí äëÿ ìîäåëèðîâàíèÿ äèíàìèêè ìî- ëåêóëÿðíûõ ñèñòåì, õàðàêòåðèçóþùèõñÿ áîëü- øèì êîëè÷åñòâîì ñëîæíûõ âçàèìîäåéñòâèé è ñâÿçåé. Íà÷èíàÿ ñ âåðñèè 4.5, â Gromacs âêëþ÷åíà ïîääåðæêà CUDA [36]. Íåñìîòðÿ íà íåêîòîðûå îãðàíè÷åíèÿ (ðàçìåð àíàëèçèðóå- ìîé ñèñòåìû íå áîëåå 200 000 àòîìîâ, çà- âèñèìîñòü îò òèïà/ìîäåëè ãðàôè÷åñêîé êàðòû, ñîâìåñòèìîñòü RAM) (http://www.gromacs.org/ Downloads/Installation_Instructions/GPUs) ïî ñðàâíåíèþ ñ ðàñ÷åòàìè íà CPU, ðåøåíèå Gromacs äëÿ GPU ïîçâîëÿåò çíà÷èòåëüíî ñî- êðàòèòü âðåìÿ ðàñ÷åòîâ [36, 37]. Ñëåäóåò îòìåòèòü, ÷òî ïðè èñïîëüçîâàíèè CUDA ìî- ãóò íàáëþäàòüñÿ íåçíà÷èòåëüíûå îòëè÷èÿ â ðåçóëüòàòàõ ðàñ÷åòîâ, âûïîëíåííûõ ñ ïîìî- ùüþ ðàçíûõ ãðàôè÷åñêèõ óñêîðèòåëåé, ÷òî ñâÿçàíî ñ èçìåíåíèÿìè, âíåñåííûìè â ðàáîòó ðÿäà àëãîðèòìîâ ñ öåëüþ àäàïòàöèè ðàáîòû Gromacs íà GPU [36]. Òàêèì îáðàçîì, â íàñòîÿùåå âðåìÿ òåõíî- ëîãèè âû÷èñëåíèé ñ ïðèìåíåíèåì ãðàôè÷åñ- êèõ ïðîöåññîðîâ âûõîäÿò íà íîâûé óðîâåíü èíòåãðàöèè ñ óæå ñóùåñòâóþùèìè òåõíîëî- ãèÿìè ñóïåðêîìïüþòèíãà (êëàñòåðíûå òåõíî- ëîãèè, ãðèä). Ñåé÷àñ â ìèðå ñóùåñòâóþò áîëåå 700 êëàñòåðîâ, ðàáîòàþùèõ íà îñíîâàíèè GPU (http://www.nvidia.ru/object/what_is_cuda_ new_ru.html). Óäà÷íûì ïðèìåðîì òàêîé âû- ÷èñëèòåëüíîé èíôðàñòðóêòóðû, èñïîëüçóþùåé ïðåèìóùåñòâà ãðàôè÷åñêèõ àäàïòåðîâ ñ ïîä- äåðæêîé òåõíîëîãèè CUDA â ñî÷åòàíèè ñ òåõíîëîãèåé ãðèä, ÿâëÿåòñÿ ïðîåêò GPUGRID. net (http://www.gpugrid.net/) [38], ïðåäñòàâ- ëåííûé ðàñïðåäåëåííûìè âû÷èñëèòåëüíûìè ðåñóðñàìè GPU ñåðâåðîâ, êîòîðûå îñíàùåíû ãðàôè÷åñêèìè ïðîöåññîðàìè îò nVidia (â òîì ÷èñëå âû÷èñëèòåëüíûõ ðåñóðñîâ ïîëüçîâàòå- ëåé ïðîåêòà). Ïðîåêò ïðåäíàçíà÷åí äëÿ âû- ïîëíåíèÿ ðåñóðñîçàòðàòíûõ ðàñ÷åòîâ ìîäåëè- ðîâàíèÿ ïîëíîàòîìíûõ ìàêðîìîëåêóëÿðíûõ ñèñòåì, ðåøåíèÿ âîïðîñîâ ìîëåêóëÿðíîé áèî- ëîãèè, áèîèíôîðìàòèêè, ìåäèöèíû, ìàòåðèà- ëîâåäåíèÿ [38], è ïðåäîñòàâëÿåò èññëåäîâà- òåëÿì íîâûé êëàññ îòíîñèòåëüíî íåäîðîãèõ, íî íå ìåíåå ýôôåêòèâíûõ ñóïåðêîìïüþòåðîâ. Âàæíîé îáëàñòüþ ñòðóêòóðíîé áèîëîãèè è áèîèíôîðìàòèêè ÿâëÿåòñÿ ìîäåëèðîâàíèå ìåæìîëåêóëÿðíûõ âçàèìîäåéñòâèé, èëè ìîëå- êóëÿðíûé äîêèíã (ñòûêîâêà). Áóäó÷è íåîòúåì- ëåìûì ýòàïîì ðàöèîíàëüíîãî äèçàéíà íîâûõ ëåêàðñòâåííûõ ïðåïàðàòîâ, áèîëîãè÷åñêè àê- òèâíûõ âåùåñòâ, ðåêîíñòðóêöèè ñòðóêòóðû ìàêðîìîëåêóëÿðíûõ êîìïëåêñîâ è ìåõàíèç- ìîâ èõ ôîðìèðîâàíèÿ [30], ìîëåêóëÿðíûé äîêèíã ÿâëÿåòñÿ íàáîðîì ñëîæíûõ ðàñ÷åòîâ (àëãîðèòìîâ) âçàèìîäåéñòâèé 3D-ñòðóêòóð áå- ëîê-áåëêîâûõ èëè ëèãàíä-áåëêîâûõ êîìïëåê- ñîâ, íà÷èíàÿ ñ ìîäåëèðîâàíèÿ îòäåëüíûõ íå- ñâÿçàííûõ ñòðóêòóð ñîîòâåòñòâóþùèõ áåëêîâ è ëèãàíäîâ [39]. Ýòî òðåáóåò ïðèìåíåíèÿ çíà- ÷èòåëüíûõ âû÷èñëèòåëüíûõ ðåñóðñîâ, òàêèõ êàê ñóïåðêîìïüþòåðû è ðàñïàðàëëåëåííûå âû- ÷èñëèòåëüíûå ñèñòåìû [40].  íàñòîÿùåå âðå- ìÿ èìåþòñÿ íåñêîëüêî ïðèìåðîâ óñïåøíî- ãî ïðèìåíåíèÿ GPU äëÿ ñîêðàùåíèÿ âðåìåíè âûïîëíåíèÿ äîêèíãà [41–43]. Òàê, åñòü äàííûå îá óñïåøíîì ïðèìåíåíèè CUDA äëÿ îïòèìè- çàöèè ðàáîòû ïðîãðàììû AutoDock [43; http:// www.vpac.org/files/OptimizingAutodockwith CUDA.pdf] (www.gpuautodock.sf.net), ðàáîòàþ- ùåé íà îñíîâå Ëàìàðêîâñêîãî ãåíåòè÷åñêîãî àëãîðèòìà (LGA) [45]. Äðóãèì ïðèìåðîì ÿâëÿåòñÿ ïàêåò Hex (http://hex.loria.fr/), ïðåäíàçíà÷åííûé äëÿ âû- ïîëíåíèÿ è âèçóàëèçàöèè ðåçóëüòàòîâ ãèáêî- ãî ìîëåêóëÿðíîãî äîêèíãà áåëêîâ è ÄÍÊ, à òàêæå æåñòêîãî äîêèíãà íèçêîìîëåêóëÿðíûõ ëèãàíäîâ è áåëêîâûõ ìèøåíåé [42, 43] íà îñíîâå ïðèìåíåíèÿ ïîëÿðíîãî àëãîðèòìà áûñ- òðûõ ïðåîáðàçîâàíèé Ôóðüå (FFT) [43]. Íà- ÷èíàÿ ñ âåðñèè 6.0, â ïàêåò Hex âêëþ÷åíà ïîääåðæêà òåõíîëîãèè CUDA [42, 43]. Ïîýòîìó öåëüþ íàøåãî èññëåäîâàíèÿ ñòàë àíàëèç ðåàëüíîãî ïðèðîñòà ñêîðîñòè âû÷èñ- ëåíèé è ïðîèçâîäèòåëüíîñòè äîêèíãà çà ñ÷åò GPU-îïòèìèçàöèè ðàáîòû ñôåðè÷åñêîãî ïîëÿðíîãî àëãîðèòìà ïðåîáðàçîâàíèé Ôóðüå, ÿâëÿþùåãîñÿ îñíîâíûì ðåñóðñîçàòðàòíûì ýòàïîì ðàñ÷åòîâ ìîëåêóëÿðíîé ñòûêîâêè â ïðîãðàììå Hex [43], ïðè èñïîëüçîâàíèè CUDA âåðñèè ïðîãðàììíîãî ïàêåòà Hex 6.1 íà ïðè- ìåðå äîêèíãà òðåõìåðíûõ ìîäåëåé íèçêîìî- ëåêóëÿðíûõ ñîåäèíåíèé êëàññîâ áåíçèìèäà- çîëîâ, äèíèòðîàíèëèíîâ è ôåíèëêàðáàìàòîâ íà ìîäåëè öèòîçîëüíîé ôîðìû ðàñòèòåëüíîãî áåëêà FtsZ2-2 (UniProt: Q9LXJ0, At3g52750) èç Arabidopsis thaliana [46]. Ìàòåðèàëû è ìåòîäû. Ìîëåêóëÿðíûé äî- êèíã îñóùåñòâëÿëè ñ èñïîëüçîâàíèåì ðàíåå 58 ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2012. ¹ 3 Î.Í. Äåì÷óê, Ï.À. Êàðïîâ, ß.Á. Áëþì ðåêîíñòðóèðîâàííîé íàìè ìîäåëè öèòîçîëü- íîé ôîðìû ðàñòèòåëüíîãî áåëêà FtsZ2-2 èç Arabidopsis thaliana [47] è òðåõìåðíûõ ìîäå- ëåé íèçêîìîëåêóëÿðíûõ ñîåäèíåíèé êëàññà áåíçèìèäàçîëîâ – áåíîìèëà (ìåòèë-N-[1-(áó- òèëêàðáàìîèë)áåíçèìèäàçîë-2-èë]êàðáà- ìàò) (CID: 28780), íîêîäàçîëà (ìåòèë-N-[6- (òèîôåí-2-êàðáîíèë)-1H-áåíçèìèäàçîë- 2-èë]êàðáàìàò) (CID: 4122) è ÷åòûðåõ 2,5,6-òðåõ- çàìåùåííûõ áåíçèìèäàçîëîâ, êîòîðûå îêà- çàëèñü ëèäåðàìè ïî àíòèáàêòåðèàëüíîé àê- òèâíîñòè â èññëåäîâàíèÿõ ãðóïïû È. Îäæèìû – 1a-G4, 1a-G7, 1b-G1 è 1b-G2 [48], à òàêæå ïðåäñòàâèòåëåé äèíèòðîàíèëèíîâ: îðèçàëèíà (4-(äèïðîïèëàìèíî)-3,5-äèíèòðîáåíçåí- ñóëüôîíàìèä) (CID: 29393), ïåíäèìåòàëèíà (3,4-äèìåòèë-2,6-äèíèòðî-N-ïåíòàí-3-èëà- íèëèí) (CID: 38479), òðèôëþðàëèíà (2,6-äè- íèòðî-N,N-äèïðîïèë-4-(òðèôòîðìåòèë) àíèëèí) (CID: 5569) è ýòàëôëþðàëèíà (N-ýòèë- N-(2-ìåòèëïðîï-2-ýíèë)-2,6-äèíèòðî-4- (òðèôòîðìåòèë)àíèëèí) (CID: 41381) è ñîåäè- íåíèé êëàññà ôîñôîðîàìèäîâ – àìèïðîôîñ- ìåòèëà (N-[ìåòîêñè-(4-ìåòèë-2-íèòðîôåíîê- ñè)ôîñôèíîòèîë]-ïðîïàí-2-àìèí) (CID: 100524) è êðåìàðòà (N-[ýòîêñè-(5-ìåòèë-2-íèòðîôåíîê- ñè)ôîñôèíîòèîë]áóòàí-2-àìèí) (CID: 37419). Èñõîäíûå ìîäåëè ïðîñòðàíñòâåííûõ ñòðóê- òóð ãåðáèöèäîâ âçÿòû èç ðåïîçèòîðèÿ áàçû äàííûõ «PubChemCompound» (NCBI – http:// www.ncbi.nlm.nih.gov/pccompound/) [49]. Ôàé- ëû êîîðäèíàò òðåõçàìåùåííûõ áåíçèìèäàçî- ëîâ, êàê è ôàéëû òîïîëîãèè âñåõ èñïîëü- çóåìûõ ëèãàíäîâ, ïîëó÷åíû ñ ïîìîùüþ ñåð- âåðà PRODRG2 (http://davapc1.bioch.dundee. ac.uk/prodrg/) [50]. Âû÷èñëèòåëüíûé ñåðâåð ñîáðàëè íà îñíîâå ìàòåðèíñêîé ïëàòû ASUS P5K-SE/EPU (www. asus.com), ïîñòðîåííîé íà ÷èïñåòå Intel P35 (www.intel.com) ïëàòôîðìû LGA775 (FC- LGA6), ñ èíñòàëëÿöèåé 4 Ãá îïåðàòèâíîé ïà- ìÿòè Kingston DDR2-SDRAM 400 ÌÃö.  êà÷åñòâå CPU èñïîëüçîâàëè öåíòðàëüíûé ïðî- öåññîð Intel Core 2 Quad Q6600 (2400 ÌÃö), èìåþùèé ÷åòûðå ëîãè÷åñêèõ ÿäðà ñ îáúåìàìè êýøåé L1 êîäà, L1 äàííûõ è L2, ðàâíûìè 32 Êá, 32 Êá è 2×4096 Ìá ñîîòâåòñòâåííî, è ïîääåðæèâàþùèé íàáîðû èíñòðóêöèé x86, x86-64, MMX, SSE, SSE2, SSE3, SSSE3 (http://ark.intel.com/). Ïðè âûïîëíåíèè ìîëåêóëÿðíûõ ðàñ÷åòîâ èñïîëüçîâàëè âèäåîàäàïòåðû ASUS EN9800GT (www.asus.com) è ZOTAC GeForce GTX 470 (www.zotac.com), ðàáîòàþùèå â ïðîãðàììíîé ñðåäå 32-áèòíîé âåðñèè ïàêåòà äëÿ ðàçðà- áîò÷èêîâ «cudatoolkit 3.2.7 win32» è «cuda- toolkit 3.2.16 win32» ñîîòâåòñòâåííî. Âèäåî- àäàïòåð ASUS EN9800GT ïîñòðîåí íà ÷èïñåòå nVIDIA GeForce® 9800 GT è îñíàùåí 512 Má îïåðàòèâíîé ïàìÿòè GDDR3 SDRAM ñ ðàç- ðÿäíîñòüþ 256-áèò. ×àñòîòà ïàìÿòè ñîñòàâëÿåò 1800 ÌÃö ñ ïîëîñîé ïðîïóñêàíèÿ 57,6 Ãá/ñ. Ýòà âèäåîêàðòà èìååò 112 Stream-ïðîöåññî- ðîâ, õàðàêòåðèçóåòñÿ ÷àñòîòîé ÿäðà 1200 ÌÃö è ÷àñòîòîé øåéäåðíîãî áëîêà 1500 ÌÃö ñî ñêîðîñòüþ íàëîæåíèÿ òåêñòóð 33,6 ìëðä òåê- ñåëåé çà 1 ñ. Âèäåîàäàïòåð ZOTAC GeForce GTX 470 ïîñòðîåí íà ÷èïñåòå nVIDIA GeForce® GTX 470 è îñíàùåí 1280 Má îïå- ðàòèâíîé ïàìÿòè GDDR5 SDRAM ñ ðàç- ðÿäíîñòüþ 320-áèò, êîòîðàÿ ðàáîòàåò íà ÷àñ- òîòå 3348 ÌÃö ñ ïðîïóñêíîé ñïîñîáíîñòüþ 133,9 Ãá/ñ. Âèäåîêàðòà èìååò 448 Stream- ïðîöåññîðîâ, ðàáîòàþùèõ íà ÷àñòîòå 1215 ÌÃö ñî ñêîðîñòüþ íàëîæåíèÿ òåêñòóð 34 ìëðä òåê- ñåëåé çà 1 ñ. Äîêèíã íèçêîìîëåêóëÿðíûõ ñîåäèíåíèé ðàññ÷èòûâàëè ïóòåì ïîî÷åðåäíîãî èñïîëüçî- âàíèÿ âû÷èñëèòåëüíûõ ìîùíîñòåé öåíòðàëü- íîãî ïðîöåññîðà (CPU ðåæèì) è âèäåîàäàï- òåðîâ (GPU ðåæèì), óñòàíîâëåííûõ íà óêà- çàííóþ ïëàòôîðìó. Æåñòêèé äîêèíã [51] âûïîëíÿëè ñ èñïîëü- çîâàíèåì ïðîãðàììíîãî ïàêåòà Hex 6.1 (http:// hex.loria.fr/) [43, 52] ïðè ïîääåðæêå òåõíî- ëîãèè CUDA (http://www.nvidia.com/), êîòî- ðûé ïîçâîëÿåò ïðîâîäèòü âû÷èñëåíèÿ êàê â CPU, òàê è â GPU ðåæèìàõ [43]. Ïðè âû- ïîëíåíèè ðàñ÷åòîâ âî âñåõ âàðèàíòàõ èñ- ïîëüçîâàëè ñòàíäàðòíûé íàáîð ïàðàìåòðîâ êîíòðîëÿ (ïóíêò «Docking» èç ìåíþ «Con- trols»): Correlation Type – Shape + Electrostatic; FFT Mode – 3D; Post Processing – None; Grid Dimensions – 0.5 Å; Distance Range – 60 Å; Scan Step – 0.5 Å; Solutions – 500. Ïàðà- ìåòð FFT Mode-3D ñâèäåòåëüñòâóåò îá èñ- ïîëüçîâàíèè â ïðîöåññå äîêèíãà àëãîðèòìà áûñòðîãî ïðåîáðàçîâàíèÿ Ôóðüå (FFT – fast Fourier transform) â ðåæèìå òðåõìåðíîé êîð- ðåëÿöèè ïî ôîðìå è ýëåêòðîñòàòè÷åñêîìó 59ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2012. ¹ 3 Äîêèíã íèçêîìîëåêóëÿðíûõ ëèãàíäîâ íà ìîëåêóëå ðàñòèòåëüíîãî FtsZ-áåëêà âçàèìîäåéñòâèþ. Óñòàíîâêè ïàðàìåòðà Solu- tions ïîçâîëÿþò ñîõðàíÿòü èíôîðìàöèþ î ïåðâûõ 500 îðèåíòàöèÿõ ëèãàíäà [42, 53]. Îñòàëüíûå ïàðàìåòðû ïàêåòà Hex èñïîëüçî- âàëè â ðåæèìå ïî óìîë÷àíèþ (http://hex.loria. fr/manual/hex_manual.html). Ðåçóëüòàòû èññëåäîâàíèé è èõ îáñóæäåíèå. Âëèÿíèå àïïàðàòíîé ïëàòôîðìû íà ñêîðîñòü ìîëåêóëÿðíûõ âû÷èñëåíèé. Àíàëèç ëîã-ôàé- ëîâ ïðîöåññà äîêèðîâàíèÿ â ïðîãðàììå Hex 6.1 ïîçâîëÿåò âûäåëèòü äâà îñíîâíûõ ýòàïà, êîòîðûå â ñâîþ î÷åðåäü ìîæíî ðàçäåëèòü åùå íà íåñêîëüêî ïîäýòàïîâ.  òå÷åíèå ïåð- âîãî ýòàïà ïðîèñõîäèò êîíòóðèðîâàíèå ïî- âåðõíîñòåé ìîëåêóë áåëêà-ìèøåíè (FtsZ2-2 èç Arabidopsis thaliana) è ëèãàíäà, îòáîð ïî- âåðõíîñòåé ìîëåêóë, èõ âíóòðåííèõ îáúåìîâ, à òàêæå ÷åòûðåõêðàòíûé ðàñ÷åò êîýôôèöèåí- òîâ ïîâåðõíîñòåé ïðè ñòàíäàðòíîì çíà÷åíèè (N = 25) óðîâíÿ ïðîñòðàíñòâåííîé (3D) äå- òàëèçàöèè. Âòîðîé ýòàï çàêëþ÷àåòñÿ â ïîèñêå âîç- ìîæíûõ ïðîñòðàíñòâåííûõ îðèåíòàöèé ëè- ãàíäà îòíîñèòåëüíî ïîâåðõíîñòè áåëêà ñ èñ- ïîëüçîâàíèåì 3D àëãîðèòìà áûñòðûõ ïðå- îáðàçîâàíèé Ôóðüå (3D FFT) [43] è îöåíêå êàæäîé èç ñãåíåðèðîâàííûõ êîíôîðìàöèé ëè- ãàíäà â ñîñòàâå êîìïëåêñà. Ïîñëåäóþùèé ïðî- öåññ âêëþ÷àåò ðàñ÷åò êîýôôèöèåíòà âåêòîðà ðîòàöèè, çàïóñê ïðîöåññà âåðèôèêàöèè è îöåí- êó âûáîðêè êîíôîðìàöèé, ïîëó÷åííûõ â ðå- çóëüòàòå ðàáîòû àëãîðèòìà îäíîìåðíûõ (1-D) áûñòðûõ ïðåîáðàçîâàíèé Ôóðüå (1D FFT) [43]. Íà ãèñòîãðàììå ïîêàçàíî âðåìÿ âûïîëíå- íèÿ (ýòàïû) äîêèíãà ïðè èñïîëüçîâàíèè ðàç- íûõ àïïàðàòíûõ ïëàòôîðì êàê ñ èñïîëüçîâà- íèåì ÿäåð öåíòðàëüíîãî ïðîöåññîðà (CPU), òàê è ãðàôè÷åñêèõ óñêîðèòåëåé (GPU) ðàçíûõ ïîêîëåíèé. Îñíîâíîå âðåìÿ âûïîëíåíèÿ ïåð- âîãî ýòàïà ïðèõîäèòñÿ íà ðàñ÷åò êîýôôè- öèåíòîâ ïîâåðõíîñòåé, ïîñêîëüêó ïðåäøåñò- âóþùèå ïîäãîòîâèòåëüíûå ñòàäèè äëÿòñÿ î÷åíü êîðîòêèé ïðîìåæóòîê âðåìåíè – ïîðÿäêà íå- ñêîëüêèõ ñåêóíä – è íå âíîñÿò ñóùåñòâåííîãî âêëàäà â îáùåå âðåìÿ ðàñ÷åòà äîêèíãà. Óñòà- íîâëåíî, ÷òî âûïîëíåíèå îòäåëüíûõ ñòàäèé ïåðâîãî ýòàïà õàðàêòåðèçóåòñÿ îäèíàêîâîé äëèòåëüíîñòüþ êàê ïðè ðàñ÷åòàõ íà CPU, òàê è GPU. Ó÷èòûâàÿ íåçíà÷èòåëüíóþ îáùóþ ïðîäîëæèòåëüíîñòü ïåðâîãî ýòàïà ïî ñðàâíå- íèþ ñî âòîðûì (â ñðåäíåì 35 ñ ïðîòèâ 30–35 ìèí â ñëó÷àå ñ CPU è 2–4 ìèí â ñëó÷àå ñ GPU), ìîæíî ñäåëàòü âûâîä îá îòñóòñòâèè ñó- ùåñòâåííûõ ïðåèìóùåñòâ èñïîëüçîâàíèÿ ãðà- ôè÷åñêèõ ïðîöåññîðîâ ïðè ïðîâåäåíèè ðàñ÷å- òîâ íà ïåðâîì ýòàïå äîêèíãà. Êàê áûëî îòìå÷åíî, âòîðîé ýòàï (ðèñó- íîê) ïðåäñòàâëåí äâóìÿ ïîäýòàïàìè: 1) ïî- Ñðàâíåíèå äëèòåëüíîñòè âûïîëíåíèÿ îòäåëüíûõ îïåðàöèé ñ ïîìîùüþ ïðîãðàììíîãî ïàêåòà Hex 6.1 âî âðåìÿ ðàñ÷åòîâ äîêèíãà íèçêîìîëåêóëÿðíûõ ëèãàíäîâ íà ìîëåêóëå FtsZ áåëêà ñ èñïîëüçîâàíèåì âû- ÷èñëèòåëüíîé ìîùíîñòè ÿäðà öåíòðàëüíîãî ïðîöåññîðà (CPU) è ÿäåð ãðàôè÷åñêèõ óñêîðèòåëåé (GPU): ïî âåðòèêàëè – âðåìÿ ðàñ÷åòà, ñ; ïî ãîðèçîíòàëè – ãåðáèöèäû; 1 – GPU; 2 – GPU 9800GT; 3 – GPU 470GTX 60 ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2012. ¹ 3 Î.Í. Äåì÷óê, Ï.À. Êàðïîâ, ß.Á. Áëþì Ðåçóëüòàòû äîêèíãà íèçêîìîëåêóëÿðíûõ ëèãàíäîâ íà ìîëåêóëå ðàñòèòåëüíîãî FtsZ-áåëêà Ïðèìå÷àíèå. Eìèí – ýëåêòðîñòàòè÷åñêàÿ ýíåðãèÿ íàèëó÷øåé îðèåíòàöèè ëèãàíäà íà ïîâåðõíîñòè áåë- êà-ìèøåíè, Eìàêñ – ýëåêòðîñòàòè÷åñêàÿ ýíåðãèÿ íàèõóäøåé èç 500 îðèåíòàöèé ëèãàíäà. Ëèãàíä Óñòðîéñòâî ðàñ÷åòà Îáùåå âðåìÿ äîêèíãà Êîëè÷åñòâî íàèëó÷øèõ îðèåíòàöèé Åìèí Åìàêñ Êîëè÷åñòâî íàéäåííûõ êëàñòåðîâêÄæ/ìîëü Áåíçèìèäàçîëû Áåíîìèë Íîêîäàçîë 1a-G4 1a-G7 1b-G1 1b-G2 CPU GPU 9800GT GPU 470GTX CPU GPU 9800GT GPU 470GTX CPU GPU 9800GT GPU 470GTX CPU GPU 9800GT GPU 470GTX CPU GPU 9800GT GPU 470GTX CPU GPU 9800GT GPU 470GTX 34 ìèí, 35 ñ 4 ìèí, 30 ñ 2 ìèí, 21 ñ 33 ìèí, 43 ñ 4 ìèí, 02 ñ 2 ìèí, 19 ñ 32 ìèí, 10 ñ 3 ìèí, 47 ñ 2 ìèí, 17 ñ 31 ìèí, 8 ñ 3 ìèí, 33 ñ 2 ìèí, 10 ñ 31 ìèí, 31 ñ 3 ìèí, 36 ñ 2 ìèí, 11 ñ 32 ìèí, 17 ñ 3 ìèí, 56 ñ 2 ìèí, 16 ñ 1782 1681 1685 970 940 1002 3863 3501 3503 3110 2894 2899 2534 2419 2423 2605 2477 2479 –167,6 –167,6 –167,6 –188,1 –188,1 –183,0 –220,1 –220,1 –220,1 –206,4 –206,4 –206,4 –213,3 –213,3 –213,3 –226,6 –226,6 –226,6 –119,1 –119,7 –119,7 –140,0 –140,1 –140,0 –146,6 –115,48 –115,48 –154,5 –155,4 –155,4 –151,6 –152,1 –152,1 –160,5 –161,1 –161,1 103 102 102 55 56 56 113 113 113 116 116 116 139 139 139 126 126 126 Äèíèòðîàíèëèíû Îðèçàëèí Ïåíäèìåòàëèí Òðèôëþðàëèí Ýòàëôëþðàëèí CPU GPU 9800GT GPU 470GTX CPU GPU 9800GT GPU 470GTX CPU GPU 9800GT GPU 470GTX CPU GPU 9800GT GPU 470GTX 30 ìèí, 56 ñ 3 ìèí, 42 ñ 2 ìèí, 08 ñ 31 ìèí, 58 ñ 4 ìèí, 33 ñ 2 ìèí, 11 ñ 34 ìèí, 51 ñ 4 ìèí, 18 ñ 2 ìèí, 43 ñ 30 ìèí, 04 ñ 3 ìèí, 42 ñ 2 ìèí, 05 ñ 9718 4980 4979 3937 3130 3133 1478 1424 1429 1490 1430 1433 –293,1 –293,1 –293,1 –161,6 –161,6 –161.6 –193,6 –193,6 –193,6 –184,0 –184,0 –184,0 –186,4 –202,0 –202,0 –114,9 –116,5 –116,5 –147,2 –147,4 –147,4 –144,1 –144,6 –144,5 78 78 78 81 81 81 44 44 44 59 59 59 Ôîñôîðîàìèäû Àìèïðîôîñìåòèë Êðåìàðò CPU GPU 9800GT GPU 470GTX CPU GPU 9800GT GPU 470GTX 34 ìèí, 25 ñ 4 ìèí, 34 ñ 2 ìèí, 26 ñ 29 ìèí, 58 ñ 4 ìèí, 01 ñ 2 ìèí, 51 ñ 6798 4673 4675 218 193 194 –209,8 –209,8 –209,8 –147,8 –147,8 –147,8 –141,5 –147,2 –147,2 –120,8 –121,9 –121,9 65 65 65 8 7 7 61ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2012. ¹ 3 Äîêèíã íèçêîìîëåêóëÿðíûõ ëèãàíäîâ íà ìîëåêóëå ðàñòèòåëüíîãî FtsZ-áåëêà èñê ïî 3-D àëãîðèòìó áûñòðûõ ïðåîáðà- çîâàíèé Ôóðüå (3D FFT); 2) îöåíêà îðèåí- òàöèé ëèãàíäà ïî àëãîðèòìó îäíîìåðíûõ áûñ- òðûõ ïðåîáðàçîâàíèé Ôóðüå (1D FFT). Èç-çà íåçíà÷èòåëüíîé ïðîäîëæèòåëüíîñòè (â ïðåäå- ëàõ äî 2 ñ êàê äëÿ CPU, òàê è äëÿ îáåèõ GPU) ïðè ïîñòðîåíèè ãèñòîãðàììû âðåìÿ ðàñ÷åòà êîýôôèöèåíòîâ âåêòîðîâ ðîòàöèè áûëî èñ- êëþ÷åíî. Íà îñíîâàíèè àíàëèçà ðåçóëüòàòîâ ðàñ÷åòîâ íàìè ñäåëàí âûâîä î òîì, ÷òî íàè- áîëåå ïðîäîëæèòåëüíîé è ðåñóðñîçàòðàòíîé ñòàäèåé ðàñ÷åòà äîêèíãà ÿâëÿåòñÿ 3D FFT- ïîèñê. Ïðè èñïîëüçîâàíèè CUDA èìåííî íà ýòîé ñòàäèè äîêèíãà ðÿäà íèçêîìîëåêóëÿðíûõ ñîåäèíåíèé íà ìîëåêóëå ðàñòèòåëüíîãî áåëêà FtsZ2-2 èç A. thaliana ïðîèñõîäèò çíà÷è- òåëüíûé ïðèðîñò ïðîèçâîäèòåëüíîñòè ðàñ÷å- òîâ çà ñ÷åò ñóùåñòâåííîãî (â ñðåäíåì â 8 ðàç) ñîêðàùåíèÿ âðåìåíè ðàñ÷åòà. Òàê, ïðè èñïîëüçîâàíèè öåíòðàëüíîãî ïðîöåññîðà îá- ùåå âðåìÿ ðàñ÷åòà äîêèíãà ñîñòàâëÿåò îò 30 äî 35 ìèí, òîãäà êàê èñïîëüçîâàíèå ðåæèìà CUDA ñîêðàùàåò ýòî âðåìÿ äî 2–4,5 ìèí â çàâèñèìîñòè îò èñïîëüçóåìîãî âèäåîàäàïòåðà. Íåñìîòðÿ íà òî, ÷òî êîëè÷åñòâî ïðîöåññîðîâ â ÷èïñåòå 470GTX â 4 ðàçà áîëüøå, ÷åì â ÷èïñåòå 9800GT, ïåðåõîä íà áîëåå íîâûé ãðàôè÷åñ- êèé óñêîðèòåëü îáåñïå÷èâàåò ïðèðîñò ïðîèç- âîäèòåëüíîñòè äîêèíãà âñåãî â 1,5–2 ðàçà. Îöåíêà è àíàëèç ðåçóëüòàòîâ äîêèíãà. Ïî óñëîâèÿì äîêèíãà ïðîãðàììà Hex ñîõðàíÿëà òîëüêî ïåðâûå 500 ëó÷øèõ îðèåíòàöèé ëè- ãàíäà. Ýòè îðèåíòàöèè îðãàíèçóþòñÿ â êëàñ- òåðû, êàæäûé èç êîòîðûõ ïðåäñòàâëÿåò ñîáîé êîîðäèíàòû ëèãàíäà íà ïîâåðõíîñòè áåëêà- ìèøåíè â îäíîì èç âîçìîæíûõ ïîëîæåíèé. Êàê ïîêàçàíî â òàáëèöå, ïðè äîâîëüíî áîëü- øîì êîëè÷åñòâå (500 ïîëîæåíèé) äîïóñòèìûõ îðèåíòàöèé ëèãàíäà îíè ôîðìèðóþò âñåãî 40– 140 êëàñòåðîâ.  ñëó÷àå ñ êðåìàðòîì íàéäåíî âñåãî îêîëî 200 âîçìîæíûõ îðèåíòàöèé, äëÿ êîòîðûõ äèôôåðåíöèðîâàëîñü 7–8 êëàñòåðîâ. Íàìè îáíàðóæåíû îòëè÷èÿ â êîëè÷åñòâå íàéäåííûõ ëó÷øèõ îðèåíòàöèé ëèãàíäîâ (íàè- áîëåå ñóùåñòâåííûå â ñëó÷àå îðèçàëèíà, ïåíäè- ìåòàëèíà è àìèïðîôîñìåòèëà) â çàâèñèìîñòè îò èñïîëüçóåìûõ àïïàðàòíûõ óñòðîéñòâ (òàá- ëèöà). Òàê, ïðè àíàëèçå ðåçóëüòàòîâ ðàñ÷åòîâ ñ èñïîëüçîâàíèåì öåíòðàëüíîãî ïðîöåññîðà (Intel Core 2 Quad Q6600) êîëè÷åñòâî òàêèõ îðèåíòàöèé âñåãäà áûëî âûøå ïî ñðàâíåíèþ ñ ðàñ÷åòàìè íà ãðàôè÷åñêèõ óñêîðèòåëÿõ. Ýòî ìîæíî îáúÿñíèòü íåêîòîðûìè îòëè÷èÿìè â ïðîãðàììíîì êîäå àëãîðèòìîâ, îïòèìèçè- ðîâàííûõ ïîä òåõíîëîãèþ CUDA [42, 43, 53], îäíàêî ñëåäóåò îòìåòèòü, ÷òî óïîìÿíóòûå îò- ëè÷èÿ íå âëèÿþò íà êîíå÷íûé ðåçóëüòàò ðàñ- ÷åòîâ, òàê êàê äëÿ êàæäîãî èç ÷åòûðåõ òðåõ- çàìåùåííûõ áåíçèìèäàçîëîâ è âñåõ âîñüìè ãåðáèöèäîâ ðàçëè÷íûå àïïàðàòíûå óñòðîéñ- òâà ãåíåðèðîâàëè îäèíàêîâîå êîëè÷åñòâî êëà- ñòåðîâ ñ êîíå÷íûìè ëó÷øèìè ïîçèöèÿìè ëèãàíäîâ. Êðîìå òîãî, ïðè èñïîëüçîâàíèè ïðîãðàìì- íîãî ïàêåòà Hex 6.1 äëÿ ïåðâûõ 500 îðèåíòà- öèé ëèãàíäà, êàê ïðàâèëî, íàáëþäàëè ñîâïà- äåíèå ýíåðãåòè÷åñêèõ ïîêàçàòåëåé ëó÷øåé è õóäøåé êîíôîðìàöèé, ðàññ÷èòàííûõ êàê ñ èñïîëüçîâàíèåì öåíòðàëüíîãî ïðîöåññîðà, òàê è ãðàôè÷åñêèõ óñêîðèòåëåé. Ïðè ýòîì îá- íàðóæåííûå ÷àñòíûå îòëè÷èÿ ÿâëÿþòñÿ íå- çíà÷èòåëüíûìè, è îíè íå ìîãóò ïîâëèÿòü íà êîíå÷íûå ðåçóëüòàòû ðàñ÷åòà äîêèíãà íèçêî- ìîëåêóëÿðíûõ ñîåäèíåíèé ñ ìîëåêóëîé öåëå- âîãî áåëêà. Àíàëèç ïîëó÷åííûõ òðåõìåðíûõ ìîäåëåé êîìïëåêñîâ FtsZ-ëèãàíä, ñãåíåðèðîâàííûõ ïðè ïîìîùè ïðîãðàììíîãî ïàêåòà Hex 6.1, ïî- çâîëèë íàì èäåíòèôèöèðîâàòü â ñëó÷àå áåí- çèìèäàçîëîâ íåñêîëüêî ïîòåíöèàëüíûõ ñàéòîâ èõ ñâÿçûâàíèÿ ñ ïîâåðõíîñòüþ ìîëåêóëû áåë- êà FtsZ2-2 èç A. thaliana. Ñëåäóåò îòìåòèòü, ÷òî áîëüøèíñòâî êëàñòåðîâ êàæäîãî èç áåí- çèìèäàçîëüíûõ ñîåäèíåíèé ëîêàëèçîâàíû â ðàéîíå ñïèðàëè Í7 ìåæäó N- è Ñ-êîíöåâûìè äîìåíàìè, êîòîðûé àíàëîãè÷åí èçâåñòíîìó ñàéòó ñâÿçûâàíèÿ òàêñîëà ìîëåêóëîé -òóáó- ëèíà [54].  äàëüíåéøåì âñå èäåíòèôèöèðî- âàííûå íàìè ñàéòû ïîäëåæàò îöåíêå íà ñðîä- ñòâî ñ âåùåñòâàìè áåíçèìèäàçîëüíîé ïðèðîäû. Âûâîäû. Íà ïðèìåðå äîêèíãà ðÿäà ñîåäè- íåíèé êëàññà áåíçèìèäàçîëîâ, äèíèòðîàíèëè- íîâ è ôåíèëêàðáàìàòîâ íà ìîëåêóëó áåëêà FtsZ áûëà ïîäòâåðæäåíà àóòåíòè÷íîñòü ðå- çóëüòàòîâ ðàñ÷åòîâ, âûïîëíåííûõ ñ ïîìîùüþ GPU, ðåçóëüòàòàì, ïîëó÷åííûì ñ èñïîëüçîâà- íèåì öåíòðàëüíîãî ïðîöåññîðà. Ïîêàçàíî, ÷òî èñïîëüçîâàíèå ðàñïàðàëëåëèâàíèÿ íà GPU è, â ÷àñòíîñòè, òåõíîëîãèè CUDA (nVidia – www.nvidia.com) ïîçâîëÿåò çíà÷èòåëüíî ñî- 62 ISSN 0564–3783. Öèòîëîãèÿ è ãåíåòèêà. 2012. ¹ 3 Î.Í. Äåì÷óê, Ï.À. Êàðïîâ, ß.Á. Áëþì êðàòèòü âðåìÿ, íåîáõîäèìîå äëÿ âûïîëíåíèÿ ðÿäà ìîëåêóëÿðíûõ ðàñ÷åòîâ ïðè çíà÷èòåëü- íîì ñîêðàùåíèè ñåáåñòîèìîñòè èññëåäîâà- íèé â îáëàñòè ñòðóêòóðíîé áèîëîãèè è áèî- èíôîðìàòèêè. Èäåíòèôèöèðîâàíû òàêæå ïî- òåíöèàëüíûå ñàéòû ñâÿçûâàíèÿ áåíçèìèäà- çîëîâ ñ ïîâåðõíîñòüþ ìîëåêóëû áåëêà FtsZ2-2 èç A. thaliana. O.M. Demchuk, P.A. Karpov, Ya.B. Blume DOCKING OF LOW-MOLECULAR LIGANDS ON THE PLANT FtsZ-PROTEIN WITH APPLICATION OF CUDA-ACCELERATED CALCULATIONS This article provides review and analysis of oppor- tunities for application of the CUDA technology for acceleration of computations in structural biology and bioinformatics. On the example of work with the Hex 6.1 program, comparative analysis of increase in the speed and quality of results of hard-docking of a num- ber of low-molecular compounds on the surface of the FtsZ protein from Arabidopsis thaliana was performed. Several potential benzimidazole – plant FtsZ protein binding sites were identified. Î.Ì. Äåì÷óê, Ï.À. Êàðïîâ, ß.Á. 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id nasplib_isofts_kiev_ua-123456789-126471
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
issn 0564-3783
language Russian
last_indexed 2025-12-07T18:37:20Z
publishDate 2012
publisher Інститут клітинної біології та генетичної інженерії НАН України
record_format dspace
spelling Демчук, О.Н.
Карпов, П.А.
Блюм, Я.Б.
2017-11-24T16:24:50Z
2017-11-24T16:24:50Z
2012
Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов / О.Н. Демчук, П.А. Карпов, Я.Б. Блюм // Цитология и генетика. — 2012. — Т. 46, № 3. — С. 55-64. — Бібліогр.: 54 назв. — рос.
0564-3783
DOI: 10.3103/S0095452712030048
https://nasplib.isofts.kiev.ua/handle/123456789/126471
577.112.7(577.332+004.42)
Приведен обзор и анализ возможностей применения технологии CUDA для ускорения расчетов в области структурной биологии и биоинформатики. На примере работы с программой HEX 6.1 выполнен сравнительный анализ прироста производительности и качества результатов жесткого докинга низкомолекулярных соединений различных классов на поверхности FtsZ белка из Arabidopsis thaliana. Идентифицировано несколько потенциальных сайтов связывания бензимидазолов с растительным FtsZ.
Наводиться огляд та аналіз можливостей застосування технології CUDA для прискорення обчислень в галузі структурної біології та біоінформатики. На прикладі роботи з програмою Hex 6.1 здійснено порівняльний аналіз приросту продуктивності та якості результатів жорсткого докінгу низькомолекулярних сполук різних класів на поверхні FtsZ-білка із Arabidopsis thaliana. Ідентифіковано декілька потенційних сайтів зв’язування бензімідазолів із рослинним FtsZ.
The opportunities to apply the CUDA technology for faster computations in structural biology and bioinformatics are reviewed and analyzed. Using HEX 6.1 software, we performed a comparative analysis of the efficiency and the increase in quality after CUDA application. The work was conducted on the example of rigid docking of low-molecular-weight compounds of different classes on the surface of the Arabidopsis thaliana FtsZ. Several potential binding sites of benzimidazoles to the plant FtsZ were identified.
ru
Інститут клітинної біології та генетичної інженерії НАН України
Цитология и генетика
Оригинальные работы
Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов
Докінг низькомолекулярних лігандів на поверхні рослинного FtsZ білка: застосування технології cuda для прискорення обчислень
Docking small ligands to molecule of the plant FtsZ protein: Application of the CUDA technology for faster computations
Article
published earlier
spellingShingle Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов
Демчук, О.Н.
Карпов, П.А.
Блюм, Я.Б.
Оригинальные работы
title Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов
title_alt Докінг низькомолекулярних лігандів на поверхні рослинного FtsZ білка: застосування технології cuda для прискорення обчислень
Docking small ligands to molecule of the plant FtsZ protein: Application of the CUDA technology for faster computations
title_full Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов
title_fullStr Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов
title_full_unstemmed Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов
title_short Докинг низкомолекулярных лигандов на молекуле растительного FtsZ-белка: применение технологии cuda для ускорения расчетов
title_sort докинг низкомолекулярных лигандов на молекуле растительного ftsz-белка: применение технологии cuda для ускорения расчетов
topic Оригинальные работы
topic_facet Оригинальные работы
url https://nasplib.isofts.kiev.ua/handle/123456789/126471
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AT karpovpa dockingsmallligandstomoleculeoftheplantftszproteinapplicationofthecudatechnologyforfastercomputations
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