Theoretical investigation of the interactions in binding pocket of Reverse Transcriptase

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• 作者：Kamlesh Kumar Sahu^a ; ; Nozomu Hatakeyama^b ; Akira Miyamoto^b
• 关键词：Quantum chemical molecular dynamics (QCMD) calculation ; Reverse Transcriptase ; Enzyme ; Density function theory ; Nevirapine
• 刊名：Saudi Journal of Biological Sciences
• 出版年：2015
• 出版时间：November 2015
• 年：2015
• 卷：22
• 期：6
• 页码：719-724
• 全文大小：2280 K

文摘

Interactions in proteins have been studied using several chemical information techniques including quantum chemical methods that are applied to truncated systems composed of the ligand molecule and the surrounding amino acids of the receptor. In this work we adopt an approach to study these interactions accounting for as many as possible explicit solvent molecules and without the need of a fragmented calculation. Furthermore, we embed our quantum chemical calculations within a molecular dynamics framework that enables a fundamentally fast system for quantum molecular dynamic simulations (QCMD). Central to this new system for QCMD is the tight binding QC system, newly developed in our laboratories, and which combined with the MD paradigm results in an ultra accelerated QCMD method for protein–ligand interaction evaluations. We have applied our newly developed method to the Nevirapine (NVP)–Reverse Transcriptase (RT) system. We show how the proposed method leads us to new findings. The advanced QCMD was applied to a system of RT with NVP and it has led to the knowledge of specific groups and atoms that interact with surrounding amino acids of RT and help in drug binding. The information derived from this calculation may be used in designing drugs for NVP resistant virus strains that have binding capability like NVP.