Assessing Peptide Binding to MHC II: An Accurate Semiempirical Quantum Mechanics Based Proposal.

Estimating peptide-major histocompatibility complex (pMHC) binding using structural computational methods has an impact on understanding overall immune function triggering adaptive immune responses in MHC class II molecules. We developed a strategy for optimizing pMHC structure interacting with water molecules and for calculating the binding energy of receptor + ligand systems, such as HLA-DR1 + HA, HLA-DR1 + CLIP, HLA-DR2 + MBP, and HLA-DR3 + CLIP, as well as a monosubstitution panel. Taking pMHC's structural properties, we assumed that Δ ≫ -Δ would generate a linear model for estimating relative free energy change, using three semiempirical quantum methods (PM6, PM7, and FMO-SCC-DFTB3) along with the implicit solvent models, and considering proteins in neutral and charged states.

Publisher Correction: Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Mass & secondary structure propensity of amino acids explain their mutability and evolutionary replacements.

Why is an amino acid replacement in a protein accepted during evolution? The answer given by bioinformatics relies on the frequency of change of each amino acid by another one and the propensity of each to remain unchanged. We propose that these replacement rules are recoverable from the secondary structural trends of amino acids. A distance measure between high-resolution Ramachandran distributions reveals that structurally similar residues coincide with those found in substitution matrices such as BLOSUM: Asn ↔ Asp, P™he ↔ Tyr, Lys ↔ Arg, Gln ↔ Glu, Ile ↔ Val, Met → Leu; with Ala, Cys, His, Gly, Ser, Pro, and Thr, as structurally idiosyncratic residues.

Comment on "Scaling properties of information-theoretic quantities in density functional reactivity theory" by C. Rong, T. Lu, P. W. Ayers, P. K. Chattaraj and S. Liu, Phys. Chem. Chem. Phys., 2015, 17, 4977-4988.

The scaling properties of density functionals are key for fundamentally understanding density functional theory. Accordingly, the dependence of density functionals on the number of particles is of paramount relevance. The numerical exploration by Rong et al.

Molecular model with quantum mechanical bonding information.

The molecular structure can be defined quantum mechanically thanks to the theory of atoms in molecules. Here, we report a new molecular model that reflects quantum mechanical properties of the chemical bonds. This graphical representation of molecules is based on the topology of the electron density at the critical points.

QTAIM study of an alpha-helix hydrogen bond network.

The structures of 19 alpha-helical alanine-based peptides, 13 amino acids in length, have been fully optimized using density functional theory and analyzed by means of the quantum theory of atoms in molecules. Two types of N-H..

On the local representation of the electronic momentum operator in atomic systems.

The local quantum theory is applied to the study of the momentum operator in atomic systems. Consequently, a quantum-based local momentum expression in terms of the single-electron density is determined. The limiting values of this function correctly obey two fundamental theorems: Kato's cusp condition and the Hoffmann-Ostenhof and Hoffmann-Ostenhof exponential decay.

Quantum chemical analysis explains hemagglutinin peptide-MHC Class II molecule HLA-DRbeta1*0101 interactions.

We present a new method to explore interactions between peptides and major histocompatibility complex (MHC) molecules using the resultant vector of the three principal multipole terms of the electrostatic field expansion. Being that molecular interactions are driven by electrostatic interactions, we applied quantum chemistry methods to better understand variations in the electrostatic field of the MHC Class II HLA-DRbeta1*0101-HA complex. Multipole terms were studied, finding strong alterations of the field in Pocket 1 of this MHC molecule, and weak variations in other pockets, with Pocket 1>>Pocket 4>Pocket 9 approximately Pocket 7>Pocket 6.