QSAR, DFT and molecular modeling studies of peptides from HIV-1 to describe their recognition properties by MHC-I

Abstract

Human immunodeficiency virus type-1 (HIV-1) has infected more than 40 million people around the world. HIV-1 treatment still has several side effects, and the development of a vaccine, which is another potential option for decreasing human infections, has faced challenges. This work presents a computational study that includes a quantitative structure activity relationship(QSAR) using density functional theory(DFT) for reported peptides to identify the principal quantum mechanics descriptors related to peptide activity. In addition, the molecular recognition properties of these peptides are explored on major histocompatibility complex I (MHC-I) through docking and molecular dynamics (MD) simulations accompanied by the Molecular Mechanics Generalized Born Surface Area (MMGBSA) approach for correlating peptide activity reported elsewhere vs. theoretical peptide affinity. The results show that the carboxylic acid and hydroxyl groups are chemical moieties that have an inverse relationship with biological activity. The number of sulfides, pyrroles and imidazoles from the peptide structure are directly related to biological activity. In addition, the HOMO orbital energy values of the total absolute charge and the Ghose-Crippen molar refractivity of peptides are descriptors directly related to the activity and affinity on MHC-I. Docking and MD simulation studies accompanied by an MMGBSA analysis show that the binding free energy without considering the entropic contribution is energetically favorable for all the complexes. Furthermore, good peptide interaction with the most affinity is evaluated experimentally for three proteins. Overall, this study shows that the combination of quantum mechanics descriptors and molecular modeling studies could help describe the immunogenic properties of peptides from HIV-1.

Tannic Acid-A Universal Immobilization and Fixation Agent for Nanocarbon Materials: A Novel Strategy for Aqueous Fabrication of Functional Nanocarbon Coating onto Silicon-Based Substances

“…SMD simulations were performed using Gromacs. 39 The OPLS-AA force field 40 was used for all simulations. The model of GO was set to be C 22 O(OH) 2 (COOH) 1 based on our X-ray photoelectron spectroscopy (XPS) characterization (Figure S1 and Table S1).…”

“…SMD simulations were performed using Gromacs . The OPLS-AA force field was used for all simulations.…”

Identification of peptide epitopes of the gp120 protein of HIV-1 capable of inducing cellular and humoral immunity

“…25 The search space included b-folded chains and a-helix chains of MHC following the previously published procedure. 24 A box 70 × 100 × 90 Å with a grid spacing 0.375 Å 3 was generated. Docking parameters used were 100 runs, with 100 million energy evaluations for each test, and a population size of 100 individuals.…”

NGIWY-Amide: A Bioinspired Ultrashort Self-Assembled Peptide Gelator for Local Drug Delivery Applications

“…The electronic polarizability and molar refractivity (AMR) of molecules are linked by van der Waals interactions (or London scattering attractions) (Figure 6). AMR is a constitutive additive feature that can be estimated to account for contributions from within the atom and its connectivity, as well as a variety of correction variables [31,32].…”