Amino Acid Side Chain Analogues Research Articles

Hydrogen Bonding between Amino Acid Backbone and Side Chain Analogues: A High-Level ab Initio Study

We have carried out calculations of hydrogen-bonding structures and energies, using the pseudospectral local MP2 methodology and a high-quality triple ζ basis set for a large set of amino acid side chain analogues. Both neutral and charged amino acid analogues are examined, and interactions between donors and the π electron acceptor moiety in a benzene ring are considered. A total of >140 structures have been studied, representing all possible hydrogen-bonding interactions between a set of 11 amino acid side chain analogues. The effects of electron correlation, basis set size, and basis set superposition error are analyzed in detail for this data set. A particular focus of the paper in terms of chemically interesting effects is the influence of resonance interactions upon hydrogen-bonding strength, which is elucidated quantitatively for a significant number of donor−acceptor pairs. Finally, it is observed that donors and acceptors fall into “strong” and “weak” categories, with the weak species severely da...

Energy minimization of globular proteins with solvent effects included. Comparison of empirical solvation energy terms and explicit water treatment.

The effect of an empirical solvation energy term on energy minimization of ribonuclease T1 was established using different sets of Atomic Solvation Parameters. The results are compared to minimization in vacuo and in a 10 A water shell. The best solvent model as judged from the comparison to the crystal structure was an empirical solvation potential derived from free energies of transfer of amino-acid side-chain analogues from vapour to water. The use of this model causes, however, energy and gradient oscillations, which make it inapplicable with standard protocols of molecular dynamics simulations. The empirical solvation model which was found by other authors (von Freyberg et al., 1993, J. Mol. Biol. 233, 275-292) to give good results in the NMR structure refinement led to distortions of the ribonuclease native structure. The model based on statistical analysis of crystal structures did not perform better than minimization in vacuo.

Surface Area Included in Energy Refinement of Proteins: A Comparative Study on Atomic Solvation Parameters

With the program FANTOM, we study the effect of a solvation energy term modelled by four atomic solvation parameter sets on energy refinement of proteins. Two parameter sets had previously been derived from measured free energies of transfer of hydrocarbons and amino acid side-chain analogues. Alternatively, the other two parameter sets correspond to the total or apolar accessible surface area of the protein. Twenty-five conformations of BPTI and the α-amylase inhibitor tendamistat were refined with respect to emprical energy terms (ECEPP/2) plus a solvation energy term modelled by one of the four atomic solvation parameter sets. These minimizations were compared to minimizations of the ECEPP/2 energy alone with regard to violations of upper distance limits obtained from NMR experiments as well as to root mean square deviations to NMR structures. We find that minimizations of the ECEPP/2 energy plus the total or apolar accessible surface area are superior to minimizations of the ECEPP/2 energy alone. In contrast, minimizations of the ECEPP/2 energy plus a solvation energy term based on free energies of transfer perform poorly.

Atomic solvation parameters applied to molecular dynamics of proteins in solution

A solvation energy function for use in the molecular simulation of proteins is proposed. It is based on the accessible surface areas of atoms in the protein and on atomic solvation parameters derived from empirical vapor-to-water free energies of transfer of amino acid side-chain analogs. The energy function and its derivatives were added to the CHARMM molecular simulation program (Brooks, B.R., Bruccoleri, R.E., Olafson, B.D., States, D.J., Swaminathan, S., & Karplus, M., 1983, J. Comput. Chem. 4(2), 187-217). The effect of the added energy term was evaluated by 110 ps of molecular dynamics on the 26-residue protein melittin. The melittin monomer and tetramer were studied both with and without the added term. With the added energy term the monomer partially unfolded, while the secondary structure of the tetramer was preserved, in agreement with reported experiments (Brown, L.R., Lauterwein, J., & Wuethrich, K., 1980, Biochim. Biophys. Acta 622(2), 231-244; Lauterwein, J., Brown, L.R., & Wuethrich, K., 1980, Biochim. Biophys. Acta 622(2), 219-230).

Wavelength regulation in rhodopsin: effects of dipoles and amino acid side chains.

The effects of dipoles and aromatic amino acid side-chain models on the absorption and optical activity of the rhodopsin chromophore were calculated by using perturbation theory, and the results were compared with those of a Pariser-Parr-Pople calculation for the unperturbed system. The interaction was assumed to result from purely electrostatic interactions. It was concluded that the side chains of phenylalanine and tryptophan should have no important effects. However, the charge separation in tyrosine is sufficient to cause substantial electrostatic perturbation; in fact, the effect of tyrosine is large enough to approximately many of the spectral properties of rhodopsin quantitatively. This is encouraging because the use of aromatic amino acid side-chain analogs probably provides a better physical model than the use of isolated full charges, except in the case of the counterion to the protonated Schiff base.

Solvent effects on the spectra of retinal Schiff bases--I. models for the bathochromic shift of the chromophore spectrum in visual pigments.

Abstract— Retinylidine Schiff base spectra have been investigated in a variety of solvents that were chosen primarily to mimic possible environments of the chromophore in visual pigments. These studies have identified particular amino acid side chains which can have important influences on visual pigment spectra. Most amino acid side chain analogues or solvents which mimic the peptide bond environment have little effect on retinylidine Schiff base spectra. Tyrosine, tryptophan, and cysteine analogues and ionized aspartic and glutamic acid analogues produce pronounced red shifts in the spectra. As is explained in more detail in the following paper the presence of these amino acids in the chromophore “pocket” of the protein is sufficient to account for the spectra of many visual pigments. Calculations of the spectra of protonated Schiff bases under a variety of conditions have been considered in conjunction with the spectral data to provide a model for the nature of the chromophore interactions with its environment.In solution and in rhodopsin the protonated Schiff base linkage is likely to be associated with an anion. The presence of certain amino acid side chains along the remainder of the retinal chain in the protein can modify the spectrum by altering the polarizability and polarity of the environment. The polarity in the region of the ionone ring appears to be particularly important for shifting the spectrum. In solution the nucleophilicity of the solvent also has an important influence on the anion‐protonated Schiff base region of the chromophore.