F- and V-ATPases are unique bio- and nano-molecular rotary motors among many types of bioenergy-transducing machineries. The rotational catalysis of F₁-ATPase has been investigated in detail, and the molecular mechanisms have been proposed on the basis of crystal structures of the complex and extensive single-molecule observation of the rotation. Recently, we have obtained crystal structures of bacterial V₁-ATPase (A₃B₃ and A₃B₃DF complexes) with and without nucleotide. On the basis of these new structures, we present a novel model of the rotational catalytic mechanism for V₁-ATPase, which is apparently different from those of F₁-ATPases.

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Membrane transporters transport their substrates across the membrane, thereby contributing to the maintenance of the cellular environments. One of the largest superfamily of the membrane transporters is Major Facilitator Superfamily (MFS), and many of MFS transporters are involved in the cellular uptake of various compounds utilizing the proton motive force across the membrane. Although several crystal structures of MFS transporters have been reported so far, their active transport mechanism has still remained elusive. Proton-dependent oligopeptide transporter, POT, is a member of MFS, and is involved in the uptake of oligopeptides as well as peptide-like drugs. In this article, we explain the active transporter mechanism by POT based on our recent results of the structural and computational analyses.

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Residue-residue interactions that fold a protein into a unique three-dimensional structure and make it play a specific function put structural and functional constraints in varying degrees on each residue site. Coevolution between closely-located sites caused by such selective constraints is recorded in amino acid orders of homologous sequences and also in the evolutionary trace of amino acid substitutions. A challenge for predicting residue contacts through coevolving site pairs is to extract direct dependences between sites by removing phylogenetic correlations and indirect dependences through other residues within a protein or even through other molecules. Recent attempts, particularly by detecting co-substitutions, are reviewed.

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Coupled folding and binding exhibited by intrinsically disordered proteins (IDPs) was reproduced computationally by an enhanced conformational sampling method, multicanonical molecular dynamics. We treat biomolecules with an all-atom model immersed in an explicit solvent. A free-energy landscape, which is a road map for the biomolecular conformational changes, has been computed for two IDP-partner systems (NRSF–mSin3 and pKID–KIX). Native and non-native complex clusters distributed in the landscape, and free-energy barriers separated those clusters. Analyses have suggested that various encounter complexes can reach the native complex via multiple pathways with overcoming the free-energy barriers.

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Binding of various actin binding proteins (ABPs) specifically changes the structure of the bound actin subunit (polymorphism). In some cases, those changes are propagated to the neighboring subunits within the same filament (cooperative polymorphism). If those structural changes increase the affinity of unbound subunits to that ABP, cooperative binding should occur, and in vivo, this would lead to functional differentiation of the filament. Tension also changes the structure of actin filaments, modifying the affinities for certain ABPs. Cooperative polymorphism requires intricate network of communications between and within actin subunits, which may be why this highly multifunctional protein is extremely conservative.

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