Počet záznamů: 1
On the reliability of the corrected semiempirical quantum chemical method (PM6-DH2) for assigning the protonation states in HIV-1 protease/inhibitor complexes
0368013 - UOCHB-X 2012 RIV CZ eng J - Článek v odborném periodiku
Pecina, Adam - Přenosil, Ondřej - Fanfrlík, Jindřich - Řezáč, Jan - Granatier, Jaroslav - Hobza, Pavel - Lepšík, Martin
On the reliability of the corrected semiempirical quantum chemical method (PM6-DH2) for assigning the protonation states in HIV-1 protease/inhibitor complexes.
Collection of Czechoslovak Chemical Communications. Roč. 76, č. 5 (2011), s. 457-479 ISSN 0010-0765
Grant CEP: GA MŠk LC512; GA MŠk 1M0508; GA ČR GAP208/11/0295
Výzkumný záměr: CEZ:AV0Z40550506
Klíčová slova: HIV-1 protease inhibition * protonation * QM/MM calculations
Kód oboru RIV: CF - Fyzikální chemie a teoretická chemie
Impakt faktor: 1.283, rok: 2011
A novel computational protocol for studying protonation in protein/ligand complexes is presented. We use a QM/MM approach in which the large QM part (the ligand and the active site) are treated using the corrected semiempirical method PM6-DH2, while the MM part (the rest of the protein and the surrounding solvent) are calculated using MM/GB method. This approach is applied to two model systems, the carboxylate pairs in HIV-1 protease/inhibitor complexes. The computationally more costly DFT optimizations are performed for a smaller QM part as a check of the correctness. Proton transfer (PT) phenomena occur at both the PM6-D2 and DFT levels, which underlines the requirement for a QM approach. The barriers of PT are checked in model carboxylic acid pairs using the highly accurate MP2 and CCSD(T) values. An important result of this study is the fine-tuning of the protocol which can be used in further applications; its limitations are also shown, pointing to future developments.
Trvalý link: http://hdl.handle.net/11104/0202490