An atomic charge model for graphene oxide for exploring its bioadhesive properties in explicit water.

Graphene Oxide (GO) has been shown to exhibit properties that are useful in applications such as biomedical imaging, biological sensors, and drug delivery. The binding properties of biomolecules at the surface of GO can provide insight into the potential biocompatibility of GO. Here we assess the intrinsic affinity of amino acids to GO by simulating their adsorption onto a GO surface. The simulation is done using Amber03 force-field molecular dynamics in explicit water. The emphasis is placed on developing an atomic charge model for GO. The adsorption energies are computed using atomic charges obtained from an ab initio electrostatic potential based method. The charges reported here are suitable for simulating peptide adsorption to GO.

Favorable adsorption of capped amino acids on graphene substrate driven by desolvation effect.

The use of graphene-based nanomaterials is being explored in the context of various biomedical applications. Here, we performed a molecular dynamics simulation of individual amino acids on graphene utilizing an empirical force field potential (Amber03). The accuracy of our force field method was verified by modeling the adsorption of amino acids on graphene in vacuum. These results are in excellent agreement with those calculated using ab initio methods. Our study shows that graphene exhibits bioactive properties in spite of the fact that the interaction between graphene and amino acids in a water environment is significantly weaker as compared to that in vacuum. Furthermore, the adsorption characteristics of capped and uncapped amino acids are significantly different from each other due to the desolvation effect. Finally, we conclude that when assessing protein-surface interactions based on adsorption of single amino acids, the minimum requirement is to use capped amino acids as they mimic residues as part of a peptide chain.

The search for a new model structure of beta-factor XIIa.

We present the search for a new model of beta-factor XIIa, a blood coagulation enzyme, with an unknown experimental 3D-structure. We decided to build not one but three different models using different homologous proteins as well as different techniques and different modelers. Additional studies, including extensive molecular dynamics simulations on the solvated state, allowed us to draw several conclusions concerning homology modelling, in general, and beta-factor XIIa, in particular.

Molecular mechanisms underlying differential odor responses of a mouse olfactory receptor.

The prevailing paradigm for G protein-coupled receptors is that each receptor is narrowly tuned to its ligand and closely related agonists. An outstanding problem is whether this paradigm applies to olfactory receptor (ORs), which is the largest gene family in the genome, in which each of 1,000 different G protein-coupled receptors is believed to interact with a range of different odor molecules from the many thousands that comprise "odor space." Insights into how these interactions occur are essential for understanding the sense of smell. Key questions are: (i) Is there a binding pocket? (ii) Which amino acid residues in the binding pocket contribute to peak affinities? (iii) How do affinities change with changes in agonist structure? To approach these questions, we have combined single-cell PCR results [Malnic, B., Hirono, J., Sato, T. & Buck, L. B. (1999) Cell 96, 713-723] and well-established molecular dynamics methods to model the structure of a specific OR (OR S25) and its interactions with 24 odor compounds. This receptor structure not only points to a likely odor-binding site but also independently predicts the two compounds that experimentally best activate OR S25. The results provide a mechanistic model for olfactory transduction at the molecular level and show how the basic G protein-coupled receptor template is adapted for encoding the enormous odor space. This combined approach can significantly enhance the identification of ligands for the many members of the OR family and also may shed light on other protein families that exhibit broad specificities, such as chemokine receptors and P450 oxidases.

Effects of pressure on the structure of metmyoglobin: molecular dynamics predictions for pressure unfolding through a molten globule intermediate.

We investigated the pathway for pressure unfolding of metmyoglobin using molecular dynamics (MD) for a range of pressures (0.1 MPa to 1.2 GPa) and a temperature of 300 K. We find that the unfolding of metmyoglobin proceeds via a two-step mechanism native --> molten globule intermediate --> unfolded, where the molten globule forms at 700 MPa. The simulation describes qualitatively the experimental behavior of metmyoglobin under pressure. We find that unfolding of the alpha-helices follows the sequence of migrating hydrogen bonds (i,i + 4) --> (i,i + 2).

On the hsp26 of Saccharomyces cerevisiae.

The function of the small size hsps in Saccharomyces cerevisiae has yet to be convincingly established. In this paper we present some aspects of the physiology of hsp26. Several mutant strains were analyzed with respect to the expression of the HSP26 gene using anti-hsp26 antibody for identification. The bcy1 mutant which lacks the regulating subunit of protein kinase A failed to produce full expression of HSP26 under heat shock whereas a ras2 mutation which lowers significantly the level of cAMP, produced no detectable effect. During normal growth hsp26 protein is induced during diauxie and its synthesis continues during the second exponential phase. Both BCY1 and CYR1 genes seen to be required for induction during the transition phase albeit not directly but rather interacting with some other regulatory component. The structure of hsp26 is discussed by homology with other small hsps.