Investigation of Structural Dynamics of Enzymes and Protonation States of Substrates Using Computational Tools.

This review discusses the use of molecular modeling tools, together with existing experimental findings, to provide a complete atomic-level description of enzyme dynamics and function. We focus on functionally relevant conformational dynamics of enzymes and the protonation states of substrates. The conformational fluctuations of enzymes usually play a crucial role in substrate recognition and catalysis. Protein dynamics can be altered by a tiny change in a molecular system such as different protonation states of various intermediates or by a significant perturbation such as a ligand association. Here we review recent advances in applying atomistic molecular dynamics (MD) simulations to investigate allosteric and network regulation of tryptophan synthase (TRPS) and protonation states of its intermediates and catalysis. In addition, we review studies using quantum mechanics/molecular mechanics (QM/MM) methods to investigate the protonation states of catalytic residues of β-Ketoacyl ACP synthase I (KasA). We also discuss modeling of large-scale protein motions for HIV-1 protease with coarse-grained Brownian dynamics (BD) simulations

Mechanism of PhosphoThreonine/Serine Recognition and Specificity for Modular Domains from All-atom Molecular Dynamics

<p>Abstract</p> <p>Background</p> <p>Phosphopeptide-binding domains mediate many vital cellular processes such as signal transduction and protein recognition. We studied three well-known domains important for signal transduction: BRCT repeats, WW domain and forkhead-associated (FHA) domain. The first two recognize both phosphothreonine (pThr) and phosphoserine (pSer) residues, but FHA has high specificity for pThr residues. Here we used molecular dynamics (MD) simulations to reveal how FHA exclusively chooses pThr and how BRCT and WW recognize both pThr/pSer. The work also investigated the energies and thermodynamic information of intermolecular interactions.</p> <p>Results</p> <p>Simulations carried out included wide-type and mutated systems. Through analysis of MD simulations, we found that the conserved His residue defines dual loops feature of the FHA domain, which creates a small cavity reserved for only the methyl group of pThr. These well-organized loop interactions directly response to the pThr binding selectivity, while single loop (the 2nd phosphobinding site of FHA) or in combination with α-helix (BRCT repeats) or β-sheet (WW domain) fail to differentiate pThr/pSer.</p> <p>Conclusions</p> <p>Understanding the domain pre-organizations constructed by conserved residues and the driving force of domain-phosphopeptide recognition provides structural insight into pThr specific binding, which also helps in engineering proteins and designing peptide inhibitors.</p

A mobile-device-supported peer-assisted learning system for collaborative early EFL reading

Collaborative learning methods which emphasize peer interaction have been widely applied to increase the intensity and effectiveness of EFL reading programs. However, simply grouping students heterogeneously and assigning them group goals does not guarantee that effective collaborative learning will ensue. The present research includes two studies. In Study One, the weaknesses of collaborative learning in a traditional EFL setting were observed. Then, in Study Two, a mobile-device-supported peer-assisted learning (MPAL) system was developed for the purpose of addressing the identified weaknesses. Two classes of twenty-six third grade students participated in the present research to examine the unique contribution of MPAL to collaborative EFL reading activities. The collaborative behavior of elementary EFL learners was videotaped and analyzed. Detailed analysis of the videotaped behavior indicated that MPAL helped improve collaboration in elementary school level EFL learners and promotes their reading motivation