The stability of self-assembling cyclic peptides (CPs) is attained by the intermolecular backbone-backbone hydrogen bonding (H-bonding) interactions. In addition to these H-bonding interactions, the self-assembled CPs are further stabilized by various intermolecular side chain-side chain interactions. This study investigates the role of amino acids on the structure and stability of self-assembl...

We have used a combination of simulated annealing (SA), molecular dynamics (MD) and locally enhanced sampling (LES) methods in order to predict the favourable topologies and loop conformations of dimeric DNA quadruplexes with T2 or T3 loops. This follows on from our previous MD simulation studies on the influence of loop lengths on the topology of intramolecular quadruplex structures [P. Hazel ...

Herein, we examine computationally the binding and hydrolysis reaction of the MMP-2 enzyme with two peptide substrates selected by the enzyme from a phage peptide library. Molecular dynamics simulations of the Michaelis complexes (25 ns) allow us to characterize the main enzyme/substrate contacts. Subsequently MM-PBSA calculations using independent trajectories for the complexes and the free su...

Clinical inhibitors Darunavir (DRV) and Amprenavir (APV) are less effective on HIV-2 protease (PR2) than on HIV-1 protease (PR1). To identify molecular basis associated with the lower inhibition, molecular dynamics (MD) simulations and molecular mechanics Poisson-Boltzmann surface area (MM-PBSA) calculations were performed to investigate the effectiveness of the PR1 inhibitors DRV and APV again...

Dimerization of HIV-I protease (HIV PR) monomers is an essential prerequisite for viral proteolytic activity and the subsequent generation of infectious virus particles. Disrupting dimerization of the enzyme can inhibit its activity. We have calculated the relative binding free energies between different dimers of the HIV protease using molecular dynamics and a continuum model, which we call MM...

The interaction of 278 monocyclic and bicyclic pyrimidine derivatives with human A2A adenosine receptor (AR) was investigated by employing molecular dynamics, thermodynamic analysis and three-dimensional quantitative structure-activity relationship (3D-QSAR) approaches. The binding analysis reveals that the pyrimidine derivatives are anchored in TM2, 3, 5, 6 and 7 of A2A AR by the aromatic stac...

HIV-1 reverse transcriptase (RT) is an important target for drugs used in the treatment of AIDS. Drugs known as non-nucleoside RT inhibitors (NNRTI) appear to alter the structural and dynamical properties of RT which in turn inhibit RT's ability to transcribe. Molecular dynamics (MD), principal component analysis (PCA), and binding free energy simulations are employed to explore the dynamics of...

Photoproteins are responsible for light emission in a variety of marine ctenophores and coelenterates. The mechanism of light emission in both families occurs via the same reaction. However, the arrangement of amino acid residues surrounding the chromophore, and the catalytic mechanism of light emission is unknown for the ctenophore photoproteins. In this study, we used quantum mechanics/molecu...

Tubulin is the target for many small-molecule natural compounds, which alter microtubules dynamics, and lead to cell cycle arrest and apoptosis. One of these compounds is colchicine, a plant alkaloid produced by Colchicum autumnale. While C. autumnale produces a potent cytotoxin, colchicine, and expresses its target protein, it is immune to colchicine's cytotoxic action and the mechanism of thi...

We have performed molecular dynamics simulations of the phosphorylation domain (PD) of the regulatory light chain (RLC) of smooth muscle myosin, to gain insight into the thermodynamic principles governing the phosphorylation-induced disorder-to-order transition. Simulations were performed in explicit water under near-physiological conditions, starting with an ideal alpha-helix. In the absence o...