Document Detail


Derivation of Fixed Partial Charges for Amino Acids Accommodating a Specific Water Model and Implicit Polarization.
MedLine Citation:
PMID:  23379664     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We have developed the IPolQ method for fitting non-polarizable point charges to implicitly represent the energy of polarization for systems in pure water. The method involves iterative cycles of molecular dynamics simulations to estimate the water charge density around the solute of interest followed by quantum mechanical calculations at the MP2/cc-pV(T+d)Z level to determine updated solute charges. Lennard-Jones parameters are updated starting from the Amber FF99SB nonbonded parameter set to accommodate the new charge model, guided by the comparisons to experimental hydration free energies (HFEs) of neutral amino acid side chain analogs and assumptions about the computed HFEs for charged side chains. These Lennard-Jones parameter adjustments for side chain analogs are assumed to be transferable to amino acids generally, and new charges for all standard amino acids are then derived in the presence of water modeled by TIP4P-Ew. Overall, the new charges depict substantially more polarized amino acids, particularly in the backbone moieties, than previous Amber charge sets. Efforts to complete a new force field with appropriate torsion parameters for this charge model are underway. The IPolQ method is general, applicable to arbitrary solutes.
Authors:
David S Cerutti; Julia E Rice; William Swope; David A Case
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-2-5
Journal Detail:
Title:  The journal of physical chemistry. B     Volume:  -     ISSN:  1520-5207     ISO Abbreviation:  J Phys Chem B     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-2-5     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101157530     Medline TA:  J Phys Chem B     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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