PMID- 22911614
OWN - NLM
STAT- MEDLINE
DCOM- 20130826
LR  - 20211021
IS  - 1097-0134 (Electronic)
IS  - 0887-3585 (Print)
IS  - 0887-3585 (Linking)
VI  - 81
IP  - 1
DP  - 2013 Jan
TI  - Capturing the energetics of water insertion in biological systems: the water 
      flooding approach.
PG  - 93-106
LID - 10.1002/prot.24165 [doi]
AB  - Consistent description of the effect of internal water in proteins has been a 
      major challenge for both simulation and experimental studies. Describing this 
      effect has been particularly important and elusive in cases of charges in protein 
      interiors. Here, we present a new microscopic method that provides an efficient 
      way for simulating the energetics of water insertion. Instead of performing 
      explicit Monte Carlo (MC) moves on the insertion process, which generally 
      involves an enormous number of rejected attempts, our method is based on 
      generating trial configurations with excess amount of internal water, estimating 
      the relevant free energy by the linear response approximation, and then using a 
      postprocessing MC treatment to filter out a limited number of configurations from 
      a large possible set. Our approach is validated on particularly challenging test 
      cases including the pK(a) of the V66D mutation in Staphylococcal nuclease, Glu286 
      in cytochrome c oxidase (CcO) and the energetics of a protonated water molecule 
      in the D channel of CcO. The new postprocessing method allows us to reproduce the 
      relevant energetics of highly unstable charges in protein interiors using fully 
      microscopic calculations and provides a substantial improvement over regular 
      microscopic free energy estimates. This advance established the effectiveness of 
      our water insertion strategy in challenging cases that have not been addressed 
      successfully by other microscopic methods. Furthermore, our study provides a new 
      exciting view on the crucial effect of water penetration in key biological 
      systems as well as a new view on the nature of the dielectric in protein 
      interiors.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Chakrabarty, Suman
AU  - Chakrabarty S
AD  - Department of Chemistry, University of Southern California, Los Angeles, 
      California 90089-1062, USA.
FAU - Warshel, Arieh
AU  - Warshel A
LA  - eng
GR  - R01 GM040283/GM/NIGMS NIH HHS/United States
GR  - GM40283/GM/NIGMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20120928
PL  - United States
TA  - Proteins
JT  - Proteins
JID - 8700181
RN  - 0 (Proteins)
RN  - 059QF0KO0R (Water)
SB  - IM
MH  - Algorithms
MH  - Computer Simulation
MH  - *Models, Chemical
MH  - Monte Carlo Method
MH  - Proteins/*chemistry/*metabolism
MH  - Reproducibility of Results
MH  - Thermodynamics
MH  - Water/*chemistry
PMC - PMC4545531
MID - NIHMS402625
EDAT- 2012/08/23 06:00
MHDA- 2013/08/27 06:00
PMCR- 2015/08/22
CRDT- 2012/08/23 06:00
PHST- 2012/06/11 00:00 [received]
PHST- 2012/08/07 00:00 [revised]
PHST- 2012/08/15 00:00 [accepted]
PHST- 2012/08/23 06:00 [entrez]
PHST- 2012/08/23 06:00 [pubmed]
PHST- 2013/08/27 06:00 [medline]
PHST- 2015/08/22 00:00 [pmc-release]
AID - 10.1002/prot.24165 [doi]
PST - ppublish
SO  - Proteins. 2013 Jan;81(1):93-106. doi: 10.1002/prot.24165. Epub 2012 Sep 28.