Equilibrium folding and unfolding dynamics to reveal detailed free energy landscape of src SH3 protein by magnetic tweezers

Src SH3 protein domain is a typical two-state protein which has been confirmed by research of denaturant-induced unfolding dynamics.Force spectroscopy experiments by optical tweezers and atomic force microscopy have measured the force-dependent unfolding rates with different kinds of pulling geometry.However,the equilibrium folding and unfolding dynamics at constant forces has not been reported.Here,using stable magnetic tweezers,we performed equilibrium folding and unfolding dynamic measurement and force-jump measurement of src SH3 domain with tethering points at its N-and C-termini.From the obtained force-dependent transition rates,a detailed two-state free energy landscape of src SH3 protein is constructed with quantitative information of folding free energy,transition state barrier height and position,which exemplifies the capability of magnetic tweezers to study protein folding and unfolding dynamics.

Molecular Chaperone-Dependent Polymer Translocation through Nanopores: The Effects of Chaperone Concentration and Chaperone-Polymer Interaction

The polymer translocation through a nanopore from a donor space(or named cis side) to a receiver space(trans side) in the chaperone-induced crowded environment has attracted increasing attention in recent years due to its significance in biological systems and technological applications. In this work, we mainly focus on the effects of chaperone concentration and chaperone-polymer interaction on the polymer translocation. By assuming the polymer translocation to be a quasi-equilibrium process, the free energy F of the polymer can be estimated by Rosenbluth-Rosenbluth method and then the translocation time τ can be calculated by Fokker-Plank equation based on the obtained free energy landscape. Our calculation results show that the translocation time can be controlled by independently tuning the chaperone concentration and chaperone-polymer interaction at the cis side or the trans side. There exists a critical chaperone-polymer attraction ε~*=-0.2 at which the volume exclusion and interaction effects of the chaperone can balance each other. Additionally, we also find that at large chaperone-polymer attraction, the translocation time is mainly governed by the diffusion coefficient of the polymer.

Physicochemical bases for protein folding,dynamics,and protein-ligand binding

Proteins are essential parts of living organisms and participate in virtually every process within cells. As the genomlc sequences for increasing number of organisms are completed, research into how proteins can perform such a variety of functions has become much more intensive because the value of the genomic sequences relies on the accuracy of understanding the encoded gene products. Although the static three-dimensional structures of many proteins are known, the functions of proteins are ulti- mately governed by their dynamic characteristics, including the folding process, conformational fluctuations, molecular mo- tions, and protein-ligand interactions. In this review, the physicochemical principles underlying these dynamic processes are discussed in depth based on the free energy landscape （FEL） theory. Questions of why and how proteins fold into their native conformational states, why proteins are inherently dynamic, and how their dynamic personalities govern protein functions are answered. This paper will contribute to the understanding of structure-function relationship of proteins in the post-genome era of life science research.

Atomistic simulation of the coupled adsorption and unfolding of protein GB1 on the polystyrenes nanoparticle surface

Understanding the processes of protein adsorption/desorption on nanopartieles＇ surfaces is important for the development of new nanotechnology involving biomaterials; however, an atomistic resolution picture for these processes and for the simultaneous protein conformational change is missing. Here, we report the adsorption of protein GB 1 on a polystyrene nanoparticle surface using atomistic molecular dynamic simulations. Enabled by metadynamics, we explored the relevant phase space and identified three protein states, each involving both the adsorbed and desorbed modes. We also studied the change of the secondary and tertiary structures of GB 1 during adsorption and the dominant interactions between the protein and surface in different adsorption stages. The results we obtained from simulation were found to be more adequate and complete than the previous one. We believe the model presented in this paper, in comparison with the previous ones, is a better theoretical model to understand and explain the experimental results.

Effects of a global monopole on the thermodynamic phase transition of a charged AdS black hole

We study the dynamical properties of the thermodynamic phase transition(PT)of a charged AdS black hole(BH)with a global monopole via the Gibbs free energy landscape and reveal the effects of the global monopole on the kinetics of thermodynamic PTs.First,we briefly review the thermodynamics of a charged AdS BH with a global monopole.Then,we introduce the Gibbs free energy landscape to investigate the thermodynamic stability of the BH states.Because of thermal fluctuations,the small black hole(SBH)state can transit to a large black hole(LBH)state,and vice versa.Further,we use the Fokker-Planck equation with the reflecting boundary condition to study the probability evolution of the BH state with and without a global monopole separately.It is found that for both the SBH and LBH states,the global monopole could slow down the evolution of the BH state.In addition,we obtain the relationship between the first passage time and the monopole parameterη.The result shows that as the monopole parameterηincreases,the mean first passage time becomes longer for both the SBH and LBH states.

Probing Allosteric Modulation of Membrane Receptor in the Native State by Data Mining-Integrated Tracking Microscopy

As a general mechanism for governing the bioactivity of membrane receptors,allosteric modulation is critical in cell signaling and cell communication but remains difficult to measure in situ.Herein,we introduce a data mining-integrated tracking microscopy(DMITM)to investigate allosteric modulation of membrane receptors in the native state in live cells.Using Kmeans clustering-based hidden Markov modeling to uncover the ligand binding and unbinding events with diffusivity variations of ligand-conjugated nanoprobes as observations.