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1.  MATCH: An Atom- Typing Toolset for Molecular Mechanics Force Fields 
We introduce a toolset of program libraries collectively titled MATCH (Multipurpose Atom-Typer for CHARMM) for the automated assignment of atom types and force field parameters for molecular mechanics simulation of organic molecules. The toolset includes utilities for the conversion from multiple chemical structure file formats into a molecular graph. A general chemical pattern-matching engine using this graph has been implemented whereby assignment of molecular mechanics atom types, charges and force field parameters is achieved by comparison against a customizable list of chemical fragments. While initially designed to complement the CHARMM simulation package and force fields by generating the necessary input topology and atom-type data files, MATCH can be expanded to any force field and program, and has core functionality that makes it extendable to other applications such as fragment-based property prediction. In the present work, we demonstrate the accurate construction of atomic parameters of molecules within each force field included in CHARMM36 through exhaustive cross validation studies illustrating that bond increment rules derived from one force field can be transferred to another. In addition, using leave-one-out substitution it is shown that it is also possible to substitute missing intra and intermolecular parameters with ones included in a force field to complete the parameterization of novel molecules. Finally, to demonstrate the robustness of MATCH and the coverage of chemical space offered by the recent CHARMM CGENFF force field (Vanommeslaeghe, et al., JCC., 2010, 31, 671–690), one million molecules from the PubChem database of small molecules are typed, parameterized and minimized.
doi:10.1002/jcc.21963
PMCID: PMC3228871  PMID: 22042689
Force Fields; Atom Typing; Molecular Graph; Partial Charges; Parameterization
2.  Strong asymmetric hydrogen bonding in 2-(oxamoylamino)ethyl­ammonium oxamate–oxamic acid (1/1) 
The title compound, C4H10N3O2 +·C2H2NO3 −·C2H3NO3, con­tains at least 11 distinct hydrogen-bond inter­actions showing a great variety of bond strengths. The shortest and strongest hydrogen bond [O⋯O = 2.5004 (12) Å] is found between the uncharged oxamic acid molecule and the oxamate mono­anion. The grouping formed by such a strong hydrogen bond can thus be considered as a hydrogen bis­(oxamate) monoanion. It lacks crystallographic symmetry and the two oxamate groups have different conformations, showing an asymmetric hydrogen-bond inter­action. Significantly, the asymmetry allows us to draw a direct comparison of site basicity for the two inequivalent carboxyl­ate O atoms in the planar oxamate anion. The constituent mol­ecular ions of (I) form ribbons, where all amide and carboxyl­ate groups are coplanar. Graph-set analysis of the hydrogen-bonded net­works reveals the R 2 2(10) and R 2 2(9) homodromic nets as important structure-directing motifs, which appear to be a common feature of many oxamate-containing compounds.
doi:10.1107/S0108270110004233
PMCID: PMC2855574  PMID: 20203413
3.  Coiled-Coils at the Edge of Configurational Heterogeneity. Structural Analyses of Parallel and Antiparallel Homotetrameric Coiled-Coils Reveal Configurational Sensitivity to a Single Solvent-Exposed Amino Acid Substitution.†§ 
Biochemistry  2006;45(14):4463-4473.
A detailed understanding of the mechanisms by which particular amino acid sequences can give rise to more than one folded structure, such as for proteins that undergo large conformational changes or misfolding, is a long-standing objective of protein chemistry. Here we describe the crystal structures of a single coiled-coil peptide in distinct parallel and antiparallel tetrameric configurations and further describe the parallel or antiparallel crystal structures of several related peptide sequences; the antiparallel tetrameric assemblies represents the first crystal structures of GCN4-derived peptides exhibiting such a configuration. Intriguingly, substitution of a single solvent-exposed residue enabled the parallel coiled-coil tetramer GCN4-pLI to populate the antiparallel configuration, suggesting that the two configurations are close enough in energy for subtle sequence changes to have important structural consequences. We present a structural analysis of the small changes to helix register and side chain conformations that accommodate the two configurations, and have supplemented these results using solution studies and a molecular dynamics energetic analysis using a replica exchange methodology. Considering the previous examples of structural nonspecificity in coiled-coil peptides, the findings reported here not only emphasize the predisposition of the coiled-coil motif to adopt multiple configurations, but also call attention to the associated risk that observed crytstal structures may not represent the only (or even the major) species present in solution.
doi:10.1021/bi060092q
PMCID: PMC1780269  PMID: 16584182

Results 1-3 (3)