DC和AC磁场混合作用下的离子运动

本文研讨了在微弱ＤＣ磁场和频率非常低的ＡＣ磁场并行作用下,位于大分子内部的离子运动情况。主要焦点是大分子中磁场对离子热运动的影响,通过一些离散频率的分析揭示了热运动的共振效应。指出当ＤＣ和ＡＣ磁场施加或切断时离子热运动能量将发生变化,如果大分子周围的媒介质的粒子能充分阻止瞬间接触,就会引起大分了子量子态的变化。     

Simulation of protein conformational freedom as a function of pH: constant-pH molecular dynamics using implicit titration

Solution pH is a determinant parameter on protein function and stability, and its inclusion in molecular dynamics simulations is attractive for studies at the molecular level. Current molecular dynamics simulations can consider pH only in a very limited way, through a somewhat arbitrary choice of a set of fixed charges on the titrable sites. Conversely, continuum electrostatic methods that explicitly treat pH effects assume a single protein conformation whose choice is not clearly defined. In this paper we describe a general method that combines both titration and conformational freedom. The method is based on a potential of mean force for implicit titration and combines both usual molecular dynamics and pH-dependent calculations based on continuum methods. A simple implementation of the method, using a mean field approximation, is presented and applied to the bovine pancreatic trypsin inhibitor. We believe that this constant-pH molecular dynamics method, by correctly sampling both charges and conformation, can become a valuable help in the understanding of the dependence of protein function and stability on pH. © 1997 Wiley-Liss Inc.     

Distance-based population classification software using mean-field annealing

We describe a distance-based clustering method using a proximity matrix of genetic distances to partition populations into genetically similar groupings. The optimization heuristic mean-field annealing (MFA) was used to find locally optimal solutions where exhaustive search was not possible. To illustrate this method, we analysed both simulated and real data sets. Simulated data indicated that MFA successfully differentiated population groups, even with small F(ST) values, as long as there was separation of within and between group distances. Reanalysis of microsatellite data from various human populations using mean-fields found similar ethnic groups corresponding to major geographic regions reported by Rosenberg et al. (2002) who used the model-based computer program Structure. However, with MFA, the Kalash population was found to group with other Central/South Asian populations instead of being the only member of its own genetic cluster. Europe/Middle East populations formed a separate group from Central/South Asian populations instead of being a single group in the Structure analysis. The MFA analysis determined the greatest genetic distances (largest mean intracluster distance) occurred in native American populations, identifying three groups instead of only one found with Structure. For conservation purposes, it is not only important to identify genetically similar groupings but also to determine the relative level of genetic differentiation captured within these groups. To illustrate this, we compare two separate MFA analyses of Chinook salmon (Oncorhynchus tshawytscha) populations from British Columbia, Canada. The software called PORGS-MFA used in this article can be downloaded from http://www.pac.dfo-mpo.gc.ca/science/facilities-installations/pbs-sbp/mgl-lgm/apps/porgs/index-eng.htm.     

Leukocyte integrin αLβ2 transmembrane association dynamics revealed by coarse-grained molecular dynamics simulations

Integrins are transmembrane (TM) proteins that mediate bidirectional mechanical signaling between the extracellular matrix and the cellular cytoskeletal network. Each integrin molecule consists of non-covalently associated α- and β-subunits, with each subunit consisting of a large ectodomain, a single-pass TM helix, and a short cytoplasmic tail. Previously we found evidence for a polar interaction (hydrogen bond) in the outer membrane clasp (OMC) of the leukocyte integrin αLβ2 TMs that is absent in the platelet integrin αIIβ3 OMC. Here, we compare the self-assembly dynamics of αLβ2 and αIIβ3 TM helices in a model membrane using coarse-grained molecular dynamics simulations. We found that although αIIβ3 TM helices associate more easily, packing is suboptimal. In contrast, αLβ2 TM helices achieve close-to-optimal packing. This suggests that αLβ2 TM packing is more specific, possibly due to the interhelix hydrogen bond. Theoretical association free energy profiles show a deeper minimum at a smaller helix-helix separation for αLβ2 compared with αIIβ3. The αIIβ3 profile is also more rugged with energetic barriers whereas that of αLβ2 is almost without barriers. Disruption of the interhelix hydrogen bond in αLβ2 via the β2T686G mutation results in poorer association and a similar profile as αIIβ3. The OMC polar interaction in αLβ2 thus plays a significant role in the packing of the TM helices.