Quantum binding energy features of the T3-785 collagen-like triple-helical peptide

Abstract

Collagen-based biomaterials are expected to become a useful matrix substance for various biomedical applications in the future. By taking advantage of the crystallographic data of the triple-helical peptide T3-785, a collagen-like peptide whose homotrimeric structure presents large conformational similarity to the human type III collagen, we present a quantum biochemistry study to unveil its detailed binding energy features, taking into account the inter-chain interaction energies of 90 amino acid residues distributed into three interlaced monomers. Our theoretical model is based on the density functional theory (DFT) formalism within the molecular fragmentation with conjugate caps (MFCC) approach. We predict the individual relevance (energetically) of the amino acid triplets Pro-Hyp-Gly, Ile-Thr-Gly, AlaArg-Gly and Leu-Gly-Ala, as well as the influence of the N-terminal, central and C-terminal regions, looking for the integrity of the collagen's triple helix. We found that the amino acid residues comprising the peptide T3-785 have an interaction energy that depends not only on the chemical nature of the side chain, but also the surrounding solvent molecules and inter-chain intermolecular interactions. The energy profile of this collagen-model molecule depicts a character essentially attractive to its conformational stability, encouraging research focusing on the development and synthesis of artificial collagen with high stability for bioengineering applications.

Ribosomal RNA–Aminoglycoside Hygromycin B Interaction Energy Calculation within a Density Functional Theory Framework

“…In drug–protein complexes, where attractive and repulsive interactions can be found, residues located at a distance greater than 11.0 Å from a ligand can interact strongly with it . The variety of amino acids found in proteins can present positive, negative, or neutral charges, generating greater diversity in interactions …”

“…Aiming to a computational efficiency, energetic calculations for each residue–ligand pair were done by considering the density functional theory (DFT) formalism within the local exchange–correlation energy of Perdew and Wang (LDA-PWC), accordingly to previous reports. , One well-known limitation of DFT is that it does not take into account noncovalent forces properly, which are widely found in biological systems. , To correctly describe the hydrogen bonds (h-bond) and the van der Waals (vdW) forces involved in the interaction between hygB and 30S rRNA nucleotides, we used the DFT-dispersion correction proposed by Ortmann, Bechstedt, and Schimidt (OBS) . A double numerical plus polarization (DNP) basis set was chosen to expand the Kohn–Sham orbitals, considering the electrons with unrestricted spin; the added set of polarization functions greatly improve the basis set .…”

“…26 The variety of amino acids found in proteins can present positive, negative, or neutral charges, generating greater diversity in interactions. 28 Another relevant point is that the order of energetic importance of the nucleotides for the hygB−30S complex varies very little when altering the dielectric constant ε.…”

Inhibition of the checkpoint protein PD-1 by the therapeutic antibody pembrolizumab outlined by quantum chemistry

“…Within this context, we presented here an in silico quantum biochemistry calculation of the electronic structure of the complex pembrolizumab Fab drug/PD-1 receptor in order to map its recognition surface, searching for the binding interactions that stabilize it. The quantum MFCC approach used here is a route to investigate accurately large biological systems with low computational cost, and has been applied previously to describe molecular interactions at the quantum level related to the collagen stability 35 , central nervous system disorders 36 , and breast cancer 37 , to cite just a few. There is no other quantum mechanical study relating the binding of the pembrolizumab drug at the PD-1 receptor, albeit its high pharmaceutical relevance.…”

Specific Features of Structure, Electrical Conductivity and Interlayer Adhesion of the Natural Polymer Matrix from the Layers of Branched Carbon Nanotube Networks Filled with Albumin, Collagen and Chitosan

“…The X-ray crystal structure of the peptide T3-785 at 2 Å resolution is stored in the Protein Data Bank (PDB) (the code 1BKV) [33]. Previously, by the example of this model, the conformational stability of the human type III collagen was analyzed using the DFT quantum-chemical calculations [34]. All-atom collagen system used in our work contains 1245 non-water atoms.…”