To improve computational modeling in biology, we need to deepen our understanding of water and improve our models of solvation. Explicit water models are computationally expensive and implicit water models miss much of the physics, so computer simulations of biomolecules often don't predict experiments as well as they could. We propose here a new approach to solvation that aims to be as accurate as explicit models and as fast as implicit models. We have three aims: (1) To develop 3D analytical and integral-equation approaches to compute structures and energetics of water, (2) To compare explicit with implicit solvation simulations to learn the nature of water structuring in solvation shells, and (3) To develop a Semi-Explicit method for solvation, which is faster than explicit, and more physical than implicit. Our approach is based more on the local statistical mechanics of each water molecule, rather than on continuum approximations (implicit), or brute force stochastic simulations. Our preliminary results give us optimism that this approach is working. Our model gives the density of water vs. temperature as accurately as TIP4P-Ew but 6 orders of magnitude faster. The preliminary phase diagram of water looks good. Our solvation model is capturing the free energies of solvation of neutrals and polar solutes about as accurately as explicit, and is about as fast to compute as GB. Our recent results in the blind SAMPL computational solvation modeling event are highly encouraging.

Public Health Relevance

The foundation of biological processes starts at the molecular level, and one of our key tools for understanding microscopic systems is computational modeling. Computer simulations of biomolecules often don't predict experiments as well as they could, and one of the primary reasons is limitations in the modeling of ever present water. We propose to develop new approaches for treating water that aim to deepen our understanding and lift the limitations of models for solvation.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM063592-11
Application #
8135356
Study Section
Macromolecular Structure and Function D Study Section (MSFD)
Program Officer
Preusch, Peter C
Project Start
2001-09-01
Project End
2014-08-31
Budget Start
2011-09-01
Budget End
2012-08-31
Support Year
11
Fiscal Year
2011
Total Cost
$273,415
Indirect Cost
Name
State University New York Stony Brook
Department
Chemistry
Type
Schools of Arts and Sciences
DUNS #
804878247
City
Stony Brook
State
NY
Country
United States
Zip Code
11794
Lukši?, Miha; Hribar-Lee, Barbara; Pizio, Orest (2017) Phase behaviour of a continuous shouldered well model fluid. A grand canonical Monte Carlo study. J Mol Liq 228:4-10
Brini, Emiliano; Fennell, Christopher J; Fernandez-Serra, Marivi et al. (2017) How Water's Properties Are Encoded in Its Molecular Structure and Energies. Chem Rev 117:12385-12414
Lukši?, Miha; Hribar-Lee, Barbara (2017) Volumetric and calorimetric properties of aqueous ionene solutions. J Mol Liq 228:126-132
Urbic, Tomaz (2017) Integral equation and thermodynamic perturbation theory for a two-dimensional model of chain-forming fluid. J Mol Liq 238:129-135
Urbic, Tomaz (2017) Integral equation and thermodynamic perturbation theory for a two-dimensional model of dimerising fluid. J Mol Liq 228:32-37
Urbic, Tomaz; Najem, Sara; Dias, Cristiano L (2017) Thermodynamic properties of amyloid fibrils in equilibrium. Biophys Chem 231:155-160
Kastelic, Miha; Kalyuzhnyi, Yurij V; Vlachy, Vojko (2016) Modeling phase transitions in mixtures of ?-? lens crystallins. Soft Matter 12:7289-98
Urbic, Tomaz (2016) Properties of the two-dimensional heterogeneous Lennard-Jones dimers: An integral equation study. J Chem Phys 145:194503
Brini, Emiliano; Paranahewage, S Shanaka; Fennell, Christopher J et al. (2016) Adapting the semi-explicit assembly solvation model for estimating water-cyclohexane partitioning with the SAMPL5 molecules. J Comput Aided Mol Des 30:1067-1077
Paranahewage, S Shanaka; Gierhart, Cassidy S; Fennell, Christopher J (2016) Predicting water-to-cyclohexane partitioning of the SAMPL5 molecules using dielectric balancing of force fields. J Comput Aided Mol Des 30:1059-1065

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