The Studies Of Transmembrane Proteins And Nano-materials From Molecular Dynamics Simulations

G protein coupled receptors （GPCRs） represent the largest family of membraneproteins in the human genome and richest source of targets for the pharmaceuticalindustry. GPCRs are activated by a wide variety of extracellular stimuli and interactprimarily with G proteins to trigger a cascade of responses inside the cell and GPCRsplay a crucial role in many essential physiological processes as diverse asneurotransmission, cellular metabolism, secretion, cell growth, immune defense, anddifferentiation. GPCRs are targeted by50%of marketed drugs.Recently, several crystal structures of GPCRs were reported, including Aβ₂AAdenosine Receptor（Aβ₂AAR）、Dopamine D3Receptor（D3R）、Histamine H1Receptor（H1R）、C-X-C Chemokine Receptor Type4（CXCR4）、 β₁Adrenergic Receptor （β₁AR）、β₂Adrenergic Receptor （β₂AR）, which facilitates structure-based drug discovery ofGPCRs significantly.X-ray crystallography of GPCRs furnishes a rapidly growing number of atomicresolution structures, permitting homology modeling, molecular docking and moleculardynamics simulation to reveal the physical mechanisms underlying selectivity andactivation.Here, we select three crystal structures, including D3R、H1R and β₂AR. We studythe binding mode with agonists/antagonists、 selectivity of residues and theconformational changes between agonist-bound and antagonist-bound for D3R; westudy the binding mode（binding with agonists and antagonists）、selectivity of residues、conformational change between agonist-bound and antagonist-bound for H1R and H4R;we study the sequence of conformational change of β₂AR-agonist-Gs proteinwith/without the stabilization of nano-body.Trans-membrane transporter proteins are trans-membrane proteins that control theinflux and outflux of materials across cellular membranes through high selectivity combined with high conductivity and through gating that is sensitive to essentialenvironmental factors. They as channels provide highly selective diffusive pathwaysgated by environmental factors, and as transporters furnish directed, energetically uphilltransport consuming energy. Trans-membrane transporter proteins are fundamental tothe physiology of all living organisms. The trans-membrane transporter proteins differwidely in architecture and function. Function and underlying mechanism oftrans-membrane transporter proteins are unknown due to the very limited data available.Fortunately, several crystal structures including formate transporterproteins（FocA）、multisite drug binding pocket-AcrB and Viribo cholerae concentrativenucleoside transporters （vcCNT） are reported, which facilitates underlying mechanismsdiscovery of them significantly.A rapidly growing number of crystal structures permit us to use moleculardynamics simulation to reveal the physical mechanisms underlying transporter function.Here, we study three crystal structures of trans-membrane transporter proteins. ForFocA, we first define the diameter of the entrance of the transport channel, and thenstudy the “open/closed” state of formate channel in FocA under neutral/high pH andunder low pH, study the concerted movement in FocA’s pH gating function and alsostudy the shape of the channel influenced by protonated His209or unprotonated His209.For AcrB, we first study the bound drugs, rifampicin and minocycline, which made themovement towards the extrusion funnel of ToIC; we try to identify possible fingerprintsof the peristaltic action and correlations between motions of residues and drugdisplacement, we also validate the role of Phe-617loop that played a key role in theperistaltic mechanism, and we also find that the water molecules significantlycontributed to the control of the orientation of the drug translocation.Graphene、graphene oxide （GO） and silicon （Si） nanoparticles have becomepromising materials in many fields, such as cancer therapeutics, diagnosis, imaging,drug delivery, catalysis, as well as biosensors. In order to stimulate and facilitate theseapplications, there is an urgent need for the understanding of nanopartilce toxicity andother risks involved with these nanoparticle to human health. The understanding ofinteractions between nanomaterials and biomolecules is of fundamental importance tothe area of nanobiotechnology.Here, we first select the work of interactions between graphene/graphene oxide and biomolecules: the work about chymotrypsin and trypsin adsorbed onto thegraphene/graphene oxide （GO）. We find that chymotrypsin is adsorbed onto the surfaceof both graphene and GO under different surface curvature and area. Moreover, theactive site of S1specificity pocket in chymotrypsin is far away from the graphenesurface, while it is adsorbed onto the GO surface by its cationic residues andhydrophilic residues, which strongly inhibits enzymatic activity. Moreover, the activesite of S1specificity pocket adsorption onto GO is not available for liangds with largeconformational changes, while it is available for ligand with small conformationalchange adsorbing onto the graphene. Finally, we also introduce the work about theorientation, adsorption and structure of Cytochrome C, RNase A and lysozyme adsorbedon silicon nanoparticles （SNPs） with different diameters （4nm and11nm）. Moreover,influences of different groups （-OH、-COOH、-NH₂and CH₃） coated onto siliconnanoparticles are also explored. The results are that the small SNPs induce greaterstructural stabilization, and different groups induce huge differences on structure ofproteins and enzymes.These works involved in GPCRs, transporter proteins, graphene, graphene oxideand silicon nanomaterials, will help us further study the structure、 function、mechanisms of proteins and nanomaterials.