It is shown that a long, near microsecond, atomistic simulation can shed some light upon the dynamical processes occurring in a lipid bilayer. The analysis focuses on reorientational dynamics of the chains and lateral diffusion of lipids. It is shown that the reorientational correlation functions exhibits an algebraic decay (rather than exponential) for several orders of magnitude in time. The calculated nuclear magnetic resonance relaxation rates agree with experiments for carbons at the C7 position while there are some differences for C3. Lateral diffusion can be divided into two stages. In a first stage occurring at short times, t<5 ns, the center of mass of the lipid moves due to conformational changes of the chains while the headgroup position remains relatively fixed. In this stage, the center of mass can move up to approximately 0.8 nm. The fitted short-time diffusion coefficient is D(1)=13 x 10(-7) cm(2) s(-1) On a longer time scale, the diffusion coefficient becomes D(2)=0.79 x 10(-7) cm(2) s(-1). <<<

Longxing Cao, Brian Coventry, Inna Goreshnik, Buwei Huang, William Sheffler, Joon Sung Park, Kevin M Jude, Iva Marković, Rameshwar U Kadam, Koen H G Verschueren, Kenneth Verstraete, Scott Thomas Russell Walsh, Nathaniel Bennett, Ashish Phal, Aerin Yang, Lisa Kozodoy, Michelle DeWitt, Lora Picton, Lauren Miller, Eva-Maria Strauch, Nicholas D DeBouver, Allison Pires, Asim K Bera, Samer Halabiya, Bradley Hammerson, Wei Yang, Steffen Bernard, Lance Stewart, Ian A Wilson, Hannele Ruohola-Baker, Joseph Schlessinger, Sangwon Lee, Savvas N Savvides, K Christopher Garcia, David Baker <<<

The design of proteins that bind to a specific site on the surface of a target protein using no information other than the three-dimensional structure of the target remains a challenge. Here we describe a general solution to this problem that starts with a broad exploration of the vast space of possible binding modes to a selected region of a protein surface, and then intensifies the search in the vicinity of the most promising binding modes. We demonstrate the broad applicability of this approach through the de novo design of binding proteins to 12 diverse protein targets with different shapes and surface properties. Biophysical characterization shows that the binders, which are all smaller than 65 amino acids, are hyperstable and, following experimental optimization, bind their targets with nanomolar to picomolar affinities. We succeeded in solving crystal structures of five of the binder-target complexes, and all five closely match the corresponding computational design models. Experimental data on nearly half a million computational designs and hundreds of thousands of point mutants provide detailed feedback on the strengths and limitations of the method and of our current understanding of protein-protein interactions, and should guide improvements of both. Our approach enables the targeted design of binders to sites of interest on a wide variety of proteins for therapeutic and diagnostic applications. <<<