Solvation Free Energy of Amino Acids and Side-Chain Analogues

Abstract

The solvation free energies of amino acids and their side-chain analogues in water and cyclohexane are calculated by using Monte Carlo simulation. The molecular interactions are described by the OPLS-AA force field for the amino acids and the TIP4P model for water, and the free energies are determined by using the Bennett acceptance method. Results for the side-chain analogues in cyclohexane and in water are used to evaluate the performance of the force field for the van der Waals and the electrostatic interactions, respectively. Comparison of the calculated hydration free energies for the amino acid analogues and the full amino acids allows assessment of the additivity of the side chain contributions on the number of hydrating water molecules. The hydration free energies of neutral amino acids can be reasonably approximated by adding the contributions of their side chains to that of the hydration of glycine. However, significant nonadditivity in the free energy is found for the zwitterionic form of amino acids with polar side chains. In serine and threonine, intramolecular hydrogen bonds are formed between the polar side chains and backbone groups, leading to weaker solvation than for glycine. In contrast, such nonadditivity is not observed in tyrosine, in which the hydroxyl group is farther separated from, and therefore cannot form an intramolecular hydrogen bond with, the backbone. For histidine we find that a water molecule can form a bridge when the intramolecular hydrogen bond between the polar group and the backbone is broken.

Exploring the Conserved Water Site and Hydration of a Coiled‐Coil Trimerisation Motif: A MD Simulation Study

“…The effective residence times that characterise the solvation of carbonyl oxygens show larger variations at 278 K than at 330 K. This is consistent with the above-mentioned enhanced sampling of the configurational space at 330 K. The well-converged pattern of effective residence times at 330 K, which range between 5 and 20 ps, exhibits marginal peaks for Ser1, Arg8 and Glu13. A pronounced hydration of a serine resi- www.chembiochem.org due due to its polar side chain is well known, [41,42] and the longer effective residence times for the backbone carbonyl oxygen atoms of Arg8 and Glu13 are compatible with the previously reported maxima in the water density distribution and with the position of the crystallographic water site WAT4 that is located between Arg8 and Glu13 residues of the neighbouring chains. However, the correlation between long effective residence times and maxima in the solvent density distribution is weak; prominent maxima do not imply distinctly longer residence times.…”

The x-ray absorption spectroscopy model of solvation about sulfur in aqueous L-cysteine

“…76,77 If present, the waters within this array will exchange with waters in the bulk solvent, but at some rate much slower than the bulk exchange rate. 94 If this picture is accurate, the solvation region around sulfur will include slow-exchange water molecules that can contribute some back-scattering intensity to the sulfur K-edge spectrum.…”

“…Similar water molecule networks have been reported for other dissolved aqueous amino acids. [73][74][75][76][77] Such a network would constitute an extended stable shell of water molecules about cysteine. Any durably located bridging network of hydrogen-bonded water molecules with a S Cys -O w1 -O w2 angle of 150…”

Computational Prediction of Solvation Free Energies of Amino Acids with Genetic Algorithm

“…In the optimization of the atomic parameters with genetic algorithm to calculate molecular solvation free energies, we worked with 20 amino acids for which experimental solvation energies have been reported. 24,25 All of the amino acids were subjected to the CORINA program to generate their 3-D coordinates in the Sybyl MOL2 format. 26 As implemented in CORINA, only a single conformation of each amino acid was generated based on the conformational parameters derived from the X-ray structures of small molecules.…”