Can the roles of polar and non-polar moieties be reversed in non-polar solvents?

Abstract

Using thermodynamics integration, we study the solvation free energy of 18 amino acid side chain equivalents in solvents with different polarity, ranging from the most polar water to the most...

Solvent quality and solvent polarity in polypeptides

“…The initial structures for the polypeptides were prepared using the Avogadro tool (ver 1.2.0) 30 in their extended configurations with the dihedral angles of (φ , ψ)=(180 • , 180 • ) with the N-and C-termini capped with the neutral acetate (ACE) and methylamine (NME), respectively. All the polypeptides were simulated in full atomistic details by employing the GROMOS96 (54a7) force field 31 that appears to be an optimal compromise between precision and computational cost when computing hydration enthalpies as tested against experimental data 14,32,33 . A table summarizing the amino acids used to build the homopeptides, along with their common names, and both their simplified three letters codification with the corresponding uni-letter nomenclature is shown in table 1 above.…”

“…The simulations described herein follow our previous protocol 14 . However unlike that case of single amino acid side chain equivalents, here the full atomistic polypeptide structures of different length has been considered, and the fully fledged thermodynamics integration has been carried out.…”

“…As anticipated, the aims here are twofold. First, we would like to extend our previous calculation 14 for a single amino acid side chain equivalent -a single amino acid where the backbone part of the amino acid has been replaced with a single hydrogen atom, to include the effect of the backbone as well as the dependence of the number n of included residues. Relevant questions here are possible non-linear effects of the solvation free energy as a function of the number of repeated units, and whether there is a mirror symmetry in by changing a highly polar solvent such as water H 2 O to an apolar organic solvent such as cyclohexane cC 6 H 12 .…”

Conformational Fluctuations in GTP-Bound K-Ras: A Metadynamics Perspective with Harmonic Linear Discriminant Analysis

“…Function and activity of biomolecules are dictated not only by their structure, but also by the possibility to interconvert between different metastable states. − Many proteins, for example, are known to undergo functionally relevant conformational transitions, ranging from local rearrangements to concerted motion of multiple flexible regions and to the displacement of entire domains. − Achieving an in-depth, mechanistic understanding of protein dynamics is experimentally challenging; for this reason, it is often necessary to employ molecular simulation as a predictive tool and to assist the interpretation of experimental data. The typical simulation time scale accessible with current state-of-the-art plain molecular dynamics (MD) simulations is, in many cases, significantly shorter, compared to the biologically relevant time scale. − This motivated the development of a large number methodologies to efficiently explore the conformational space, and to reconstruct the thermodynamic and kinetic properties encoded in the underlying physical model (i.e., force field). − Many of these enhanced sampling techniques rely on the construction of artificial biasing potentials acting on one or several reaction coordinate(s) or collective variable(s) (CV). − By post-processing the statistics obtained in the biased ensemble, the thermodynamic properties in the original system could be obtained.…”

Binding Thermodynamics and Interaction Patterns of Inhibitor-Major Urinary Protein-I Binding from Extensive Free-Energy Calculations: Benchmarking AMBER Force Fields

“…Replica exchange methods, − accelerated MD, umbrella sampling, − metadynamics, and nonequilibrium pulling simulations − are examples of the enhanced sampling methods. With these methods, the phase space can be effectively explored, and the postprocess reweighting procedure is used to recover the distribution of configurations in the original unbiased ensemble. − If the conformational change in the process is not the goal, but only the overall free-energy difference between different states is of interest, such as the binding affinities between protein–ligand complex, the alchemical method would make the calculation feasible. − Unlike the methods exploring the ensemble of atomic coordinates and using several important slow motions or degrees of freedom to describe the process, the alchemical method describes the process with only one order parameter, which is often termed as the alchemical order parameter. − The alchemical CV is used to define the Hamiltonian of the intermediate states, − often with the linear mixing scheme . Although the alchemical method can be efficient in computing the free-energy difference between end states, there are some technical problems.…”