Examining Electrostatic Influences on Base-Flipping:A Comparison of TIP3P and GB Solvent Models

作     者：Allyn R.Brice Brian N.Dominy 

作者机构：Department of ChemistryClemson UniversityClemsonSouth Carolina29634USA. 

出 版 物：《Communications in Computational Physics》 (计算物理通讯（英文）)

年 卷 期：2013年第13卷第1期

页      面：223-237页

核心收录：

学科分类：081704[工学-应用化学] 07[理学] 08[工学] 0817[工学-化学工程与技术] 070303[理学-有机化学] 0703[理学-化学] 

基　　金：supported by National Science Foundation Career Award MCB-0953783(to B.N.D.) 

主　　题：TIP3P generalized Born flipping implicit solvation potential of mean force DNA DNA damage 

摘      要：Recently,it was demonstrated that implicit solvent models were capable of generating stable B-form DNA ***,generalized Born(GB)implicit solvent models have improved regarding the solvation of conformational sampling of DNA[1,2].Here,we examine the performance of the GBSW and GBMV models in CHARMM for characterizing base flipping free energy profiles of undamaged and damaged DNA *** sampling of the base flipping process was performed for the bases cytosine,uracil and *** umbrella sampling simulations were carried-out with both explicit(TIP3P)and implicit(GB)solvent in order to establish the impact of the solvent model on base ***,base flipping potential of mean force(PMF)profiles generated with GB solvent resulted in a greater free energy difference of flipping than profiles generated with *** of the significant differences between implicit and explicit solvent models is the approximation of solute-solvent interactions in implicit solvent *** calculated electrostatic interaction energies between explicit water molecules and the base targeted for *** interaction energies were calculated over the base flipping reaction coordinate to illustrate the stabilizing effect of the explicit water molecules on the flipped-out *** is known that nucleic base pair hydrogen bonds also influenced the free energy of flipping since these favorable interactions must be broken in order for a base to flip-out of the *** Watson-Crick base pair hydrogen bond fractions were calculated over the umbrella sampling simulation windows in order to determine the effect of base pair interactions on the base flipping free *** is shown that interaction energies between the flipping base and explicit water molecules are responsible for the lower base flipping free energy difference in the explicit solvent PMF profiles.