A Comparative Study of the Second-Order Hydrophobic Moments for Globular Proteins: The Consensus Scale of Hydrophobicity and the CHARMM Partial Atomic Charges

Abstract

In this paper, the second-order hydrophobic moment for fifteen globular proteins in 150 nonhomologous protein chains was performed in a comparative study involving two sets of hydrophobicity: one selected from the consensus scale and the other derived from the CHARMM partial atomic charges. These proteins were divided into three groups, based on their number of residues (N) and the asphericity (δ). Proteins in Group I were spherical and those in Groups II and III were prolate. The size of the proteins is represented by the mean radius of gyration (Rg ), which follows the Flory scaling law, Rg ∝ Nν. The mean value of v was 0.35, which is similar to a polymer chain in a poor solvent. The spatial distributions of the second-order moment for each of the proteins, obtained from the two sets of hydrophobicity, were compared using the Pearson correlation coefficient; the results reveal that there is a strong correlation between the two data sets for each protein structure when the CHARMM partial atomic charges, |qi| ≥ 0.3, assigned for polar atoms, are used. The locations at which these distributions vanish and approach a negative value are at approximately 50% of the percentage of solvent accessibility, indicating that there is a transition point from hydrophobic interior to hydrophilic exterior in the proteins. This may suggest that there is a position for the proteins to determine the residues at exposed sites beyond this range.

Chemical Structure-Biological Activity Models for Pharmacophores’ 3D-Interactions

“…Recently, an extension of classical QSAR methods applied to small molecules was used to predict the interactions among macromolecules, like proteins [ 89 ]. It was noticed that the important molecular descriptors associated with significant protein–protein interactions were: the van der Waals term of the potential energy; van der Waals surface area and, also, solvent accessible surface areas calculated as an approximate sum of all hydrophobic atoms’ contributions [ 15 , 90 ]; counts of bonds from the structure of interest [ 91 ]; dipole moments, both electronic and hydrophobic [ 92 , 93 , 94 ]; and van der Waals surface areas of polar atoms and, also, hydrogen bond acceptor atoms [ 90 ]. …”

Structure–Biological Function Relationship Extended to Mitotic Arrest-Deficient 2-Like Protein Mad2 Native and Mutants-New Opportunity for Genetic Disorder Control

“…E-vdW represents the van der Waals energy as component of potential energy, vsa_hyd and ASA_hyd are considered as an approximation of the sum of van der Waals and water accessible surface areas of all hydrophobic [ 33 ]; b rigid and b rot are counts of rigid and rotatable bonds from proteins, QSAR model 3: pCR = constant + c 10 × vsa_pol + c 11 × vsa_acc + c 12 × M_dipole + c 13 × M_hyd where constant = −89.114, c 10 = +0.034, c 11 = −0.035, c 12 = +0.003, c 13 = +0.005, M_hyd and M_dipole represent hydrophobic and electronic dipole moments [ 34 ] and vsa_pol and vsa_acc are considered as approximation of the sum of the van der Waals surface areas of all polar and hydrogen bond acceptor atoms [ 33 ].…”

“…Protein hydrophobic moment is a very important descriptor, especially when conformational changes are of interest and it is considered as a sum of the product between hydrophobicity of each amino acid and their distance d i between protein centroid and the centroid of residue i in space [ 34 ]. Protein binding occurs through interactions at the molecular surface described through van der Waals and/or solvent accessible surface areas.…”

Universalities in Protein Tertiary Structures: Some New Concepts

“…Physical chemistry of polymers is rich with scaling laws, the most celebrated one being that of Flory [26][27][28][29] . Root mean square end to end distances and equivalently the radius of gyration, R G , varies as N ν where N is the number of monomeric units and ν is the scaling exponent.…”