Modifying the OPLS-AA force field to improve hydration free energies for several amino acid side chains using new atomic charges and an off-plane charge model for aromatic residues

2006 ◽  
Vol 28 (3) ◽  
pp. 689-697 ◽  
Author(s):  
Zhitao Xu ◽  
Harry H. Luo ◽  
D. Peter Tieleman
Keyword(s):  
Amino Acid ◽  
Force Field ◽  
Atomic Charges ◽  
Side Chains ◽  
Free Energies ◽  
Aromatic Residues ◽  
Charge Model ◽  
Amino Acid Side Chains

New Interaction Parameters for Charged Amino Acid Side Chains in the GROMOS Force Field

2012 ◽  
Vol 8 (10) ◽  
pp. 3705-3723 ◽  
Author(s):  
Maria M. Reif ◽  
Philippe H. Hünenberger ◽  
Chris Oostenbrink
Keyword(s):  
Amino Acid ◽  
Force Field ◽  
Interaction Parameters ◽  
Side Chains ◽  
Amino Acid Side Chains ◽  
Gromos Force Field

Peptide Backbone Effect on Hydration Free Energies of Amino Acid Side Chains

2014 ◽  
Vol 118 (46) ◽  
pp. 13162-13168 ◽  
Author(s):  
Timir Hajari ◽  
Nico F. A. van der Vegt
Keyword(s):  
Amino Acid ◽  
Side Chains ◽  
Free Energies ◽  
Peptide Backbone ◽  
Amino Acid Side Chains

scholarly journals Interactions between amino acid side chains in cylindrical hydrophobic nanopores with applications to peptide stability

2008 ◽  
Vol 105 (46) ◽  
pp. 17636-17641 ◽  
Author(s):  
S. Vaitheeswaran ◽  
D. Thirumalai
Keyword(s):  
Amino Acid ◽  
Protein Stability ◽  
Salt Bridge ◽  
Bulk Water ◽  
Side Chains ◽  
Free Energies ◽  
Cylindrical Pore ◽  
Amino Acid Side Chains ◽  
Exit Tunnel ◽  
Dynamics Simulations

Confinement effects on protein stability are relevant in a number of biological applications ranging from encapsulation in the cylindrical cavity of a chaperonin, translocation through pores, and structure formation in the exit tunnel of the ribosome. Consequently, free energies of interaction between amino acid side chains in restricted spaces can provide insights into factors that control protein stability in nanopores. Using all-atom molecular dynamics simulations, we show that 3 pair interactions between side chains—hydrophobic (Ala–Phe), polar (Ser–Asn) and charged (Lys–Glu)—are substantially altered in hydrophobic, water-filled nanopores, relative to bulk water. When the pore holds water at bulk density, the hydrophobic pair is strongly destabilized and is driven to large separations corresponding to the width and the length of the cylindrical pore. As the water density is reduced, the preference of Ala and Phe to be at the boundary decreases, and the contact pair is preferred. A model that accounts for the volume accessible to Phe and Ala in the solvent-depleted region near the pore boundary explains the simulation results. In the pore, the hydrogen-bonded interactions between Ser and Asn have an enhanced dependence on their relative orientations, as compared with bulk water. When the side chains of Lys and Glu are restrained to be side by side, parallel to each other, then salt bridge formation is promoted in the nanopore. Based on these results, we argue and demonstrate that for a generic amphiphilic sequence, cylindrical confinement is likely to enhance thermodynamic stability relative to the bulk.

Hydration Free Energies of Organic Molecules in the FreeSolv Database Calculated with Polarized Atom In Molecules Atomic Charges and the GAFF Force Field.

2018 ◽  
Author(s):  
Maximiliano Riquelme ◽  
Alejandro Lara ◽  
David L. Mobley ◽  
Toon Vestraelen ◽  
Adelio R Matamala ◽  
...  
Keyword(s):  
Force Field ◽  
Functional Groups ◽  
Electrostatic Interactions ◽  
Organic Molecules ◽  
Force Fields ◽  
Chemical Elements ◽  
Atomic Charges ◽  
Free Energies ◽  
Molecular Systems ◽  
Solvent Model

<div>Computer simulations of bio-molecular systems often use force fields, which are combinations of simple empirical atom-based functions to describe the molecular interactions. Even though polarizable force fields give a more detailed description of intermolecular interactions, nonpolarizable force fields, developed several decades ago, are often still preferred because of their reduced computation cost. Electrostatic interactions play a major role in bio-molecular systems and are therein described by atomic point charges.</div><div>In this work, we address the performance of different atomic charges to reproduce experimental hydration free energies in the FreeSolv database in combination with the GAFF force field. Atomic charges were calculated by two atoms-in-molecules approaches, Hirshfeld-I and Minimal Basis Iterative Stockholder (MBIS). To account for polarization effects, the charges were derived from the solute's electron density computed with an implicit solvent model and the energy required to polarize the solute was added to the free energy cycle. The calculated hydration free energies were analyzed with an error model, revealing systematic errors associated with specific functional groups or chemical elements. The best agreement with the experimental data is observed for the MBIS atomic charge method, including the solvent polarization, with a root mean square error of 2.0 kcal mol<sup>-1</sup> for the 613 organic molecules studied. The largest deviation was observed for phosphor-containing molecules and the molecules with amide, ester and amine functional groups.</div>

Predicting the Strength of Stacking Interactions Between Heterocycles and Aromatic Amino Acid Side Chains

2019 ◽  
Author(s):  
Andrea N. Bootsma ◽  
Analise C. Doney ◽  
Steven Wheeler
Keyword(s):  
Amino Acid ◽  
Binding Sites ◽  
Aromatic Amino Acid ◽  
Aromatic Amino Acids ◽  
Biologically Active ◽  
Side Chains ◽  
Stacking Interactions ◽  
Inhibitor Binding ◽  
Protein Binding Sites ◽  
Amino Acid Side Chains

<p>Despite the ubiquity of stacking interactions between heterocycles and aromatic amino acids in biological systems, our ability to predict their strength, even qualitatively, is limited. Based on rigorous <i>ab initio</i> data, we have devised a simple predictive model of the strength of stacking interactions between heterocycles commonly found in biologically active molecules and the amino acid side chains Phe, Tyr, and Trp. This model provides rapid predictions of the stacking ability of a given heterocycle based on readily-computed heterocycle descriptors. We show that the values of these descriptors, and therefore the strength of stacking interactions with aromatic amino acid side chains, follow simple predictable trends and can be modulated by changing the number and distribution of heteroatoms within the heterocycle. This provides a simple conceptual model for understanding stacking interactions in protein binding sites and optimizing inhibitor binding in drug design.</p>

A Strategy for Thioamide Incorporation During Fmoc Solid-Phase Peptide Synthesis with Robust Stereochemical Integrity

2019 ◽  
Author(s):  
luis camacho III ◽  
Bryan J. Lampkin ◽  
Brett VanVeller
Keyword(s):  
Amino Acid ◽  
Functional Groups ◽  
Peptide Synthesis ◽  
Solid Phase ◽  
Solid Phase Peptide Synthesis ◽  
Side Chains ◽  
Amino Acid Side Chains ◽  
Peptide Elongation

We describe a method to protect the sensitive stereochemistry of the thioamide—in analogy to the protection of the functional groups of amino acid side chains—in order to preserve the thioamide moiety during peptide elongation.<br>

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