From csbi-events at mit.edu Thu Nov 5 14:30:58 2009 From: csbi-events at mit.edu (CSBi events) Date: Thu, 5 Nov 2009 14:30:58 -0500 Subject: [CSBi-events] CSB/Biophysics Seminar tomorrow (Fri, 11/6) -- Prof. Roy Kishony Message-ID: <002601ca5e4e$80a66910$81f33b30$@edu> Fall 2009 Seminar Series on Computational and Systems Biology Friday, November 6, 2009 3:00 pm - 4:00 pm Room 32-463D Presenting: Drug interactions and their impact on the evolution of resistance Professor Roy Kishony Department of Systems Biology Harvard Medical School The application of antibiotics is hindered by a well-known "catch-22": The use of a drug promotes the emergence and spread of drug-resistant mutants that ultimately render it ineffective. While certain combination therapies are known to be more effective than single drugs, the impact of such treatments on the evolution of drug resistance is unclear. I will describe a combined theoretical-experimental approach to understand drug interactions and their effect on the evolution of resistance. Our results demonstrate how we can understand the genetic source of drug interactions and how drug interactions can be used to diminish and even invert the selection pressure for antibiotic resistance. Light refreshments to be served at 2:45 pm Host: Jeff Gore (jeffgore at gmail.com), Department of Physics -------------- next part -------------- An HTML attachment was scrubbed... URL: http://mailman.mit.edu/pipermail/csbi-events/attachments/20091105/ea6a1656/attachment.htm From csbi-events at mit.edu Fri Nov 6 16:56:25 2009 From: csbi-events at mit.edu (CSBi events) Date: Fri, 6 Nov 2009 16:56:25 -0500 Subject: [CSBi-events] CSB/Biophysics Seminar next Friday (Fri, 11/13) -- Prof. Johan Paulsson Message-ID: <005f01ca5f2b$fcb87560$f6296020$@edu> Fall 2009 Seminar Series on Computational and Systems Biology Friday, November 13, 2009 3:00 pm - 4:00 pm Room 32-463D Presenting: Understanding non-genetic heterogeneity in cells Professor Johan Paulsson Department of Systems Biology Harvard Medical School Life in single cells is dictated by chance: Reactions that involve small numbers of molecules generate spontaneous fluctuations that enslave all dependent processes. Such 'noise' can randomize developmental pathways, disrupt cell cycle control or force metabolites away from their optimal levels. It can also be exploited for advantageous heterogeneity or even for more deterministic control. I will discuss new concepts and analytical frameworks that enable us to analyze such processes, addressing many of the complications and challenges in cellular dynamics while at the same time promoting intuition and facilitating comparisons with experiments. The principles discussed will be illustrated with homeostatic feedback control, partitioning at cell division, stochastic gene expression, multimerization, and small RNAs. Light refreshments to be served at 2:45 pm Host: Alexander van Oudenaarden ( avo1 at mit.edu), Department of Physics and Biology -------------- next part -------------- An HTML attachment was scrubbed... URL: http://mailman.mit.edu/pipermail/csbi-events/attachments/20091106/1b3f73ef/attachment.htm From csbi-events at mit.edu Fri Nov 13 12:18:37 2009 From: csbi-events at mit.edu (CSBi events) Date: Fri, 13 Nov 2009 12:18:37 -0500 Subject: [CSBi-events] TODAY at 3 PM: CSB/Biophysics Seminar - Johan Paulsson Message-ID: <000601ca6485$571321a0$053964e0$@edu> Fall 2009 Seminar Series on Computational and Systems Biology Friday, November 13, 2009 3:00 pm - 4:00 pm Room 32-463D Presenting: Understanding non-genetic heterogeneity in cells Professor Johan Paulsson Department of Systems Biology Harvard Medical School Life in single cells is dictated by chance: Reactions that involve small numbers of molecules generate spontaneous fluctuations that enslave all dependent processes. Such 'noise' can randomize developmental pathways, disrupt cell cycle control or force metabolites away from their optimal levels. It can also be exploited for advantageous heterogeneity or even for more deterministic control. I will discuss new concepts and analytical frameworks that enable us to analyze such processes, addressing many of the complications and challenges in cellular dynamics while at the same time promoting intuition and facilitating comparisons with experiments. The principles discussed will be illustrated with homeostatic feedback control, partitioning at cell division, stochastic gene expression, multimerization, and small RNAs. Light refreshments to be served at 2:45 pm Host: Alexander van Oudenaarden ( avo1 at mit.edu), Departments of Physics and Biology -------------- next part -------------- An HTML attachment was scrubbed... URL: http://mailman.mit.edu/pipermail/csbi-events/attachments/20091113/c5b570b9/attachment.htm From csbi-events at mit.edu Tue Nov 17 11:25:56 2009 From: csbi-events at mit.edu (CSBi events) Date: Tue, 17 Nov 2009 11:25:56 -0500 Subject: [CSBi-events] Tomorrow: Seminar Michael Levitt 5 PM, Rm. 66-110 Message-ID: <003f01ca67a2$a4ec1a60$eec44f20$@edu> RECENT ADVANCES IN COMPUTATIONAL STRUCTURAL BIOLOGY Michael Levitt Department of Structural Biology and Computer Science Stanford University WEDNESDAY, NOVEMBER 18, 2009 5:00 PM Building 66, Room 110 (Reception at 4:30 PM in lobby area of Room 66-110.) This talk covers two topics selected from many that occupy us in the Computational Structural Biology group at Stanford: Mesoscale Modeling of Macromolecular Machines and The Nature of the Protein Universe. Both topics are my own work. Mesoscale Modeling of Macromolecular Machines. Most of the central biological functions of iving cells are performed by large complexes of individual protein domains, whose movement plays a crucial role in their biological function. I present a unique approach to this motion based on normal modes calculated in torsional angle space. Special problems arise because (1) systems are large mandating use of simplified representations; (2) modes must be calculated at an energy minimum mandating the use of accurate energy functions and convergent minimizers; (3) numerical accuracy mandates the use of complex step derivatives; (4) there are many independent molecules mandating combination of rigid body and internal degrees of freedom; and (5) resulting matrices are badly ill-conditioned mandating special eigenvalue methods. The Nature of the Protein Universe. After a decade of serious structure-determination and sequencing efforts there are over 50,000 structures and over 6 million protein sequences; an overview of the set of all proteins of all organisms is becoming an essential roadmap. Here I analyze the protein universe in terms of sequence families that have single or multi-domain architectures, with or without known structures. Growth of single domain families has saturated: almost all growth comes from multi-domain architectures that are combinations of about 25,000 domains. Multi-domain architectures, which are specific to the major groups of organisms, account for species diversity. There are known structures for a quarter of the single domain families and half of all sequences can be partially modeled due to their membership in these families. -------------- next part -------------- An HTML attachment was scrubbed... URL: http://mailman.mit.edu/pipermail/csbi-events/attachments/20091117/5555937b/attachment.htm From csbi-events at mit.edu Wed Nov 18 23:17:56 2009 From: csbi-events at mit.edu (CSBi events) Date: Wed, 18 Nov 2009 23:17:56 -0500 Subject: [CSBi-events] Friday 11/20 at 3 PM: CSB/Biophysics Seminar - Samy Meroueh Message-ID: <000601ca68cf$46b77e70$d4267b50$@edu> Fall 2009 Seminar Series on Computational and Systems Biology Friday, November 20, 2009 3:00 pm - 4:00 pm Room 32-463D Presenting: Computational Design of Molecules that Modulate Interactions Critical in Tumor Invasion and Metastasis Professor Samy Meroueh Department of Biochemistry and Molecular Biology and Center for Computational Biology Indiana University School of Medicine The urokinase receptor (uPAR) is a GPI-anchored cell surface receptor that focuses proteolysis at the cell surface through its association with the serine protease urokinase (uPA). In addition, uPAR activates cell surface receptors that include integrins, receptor tyrosine kinases (RTKs) and G-coupled protein receptors (GPCRs). A large body of evidence has implicated these interactions with tumor invasion and metastasis. A computational search through molecular docking is conducted to target multiple sites on uPAR in an effort to simultaneously shut down its proteolytic and signaling capabilities. A number of molecules were found to bind to the receptor as established through biochemical assays. In cell culture, compounds revealed inhibition of MDA-MB-231 breast tumor cell adhesion, migration, invasion, angiogenesis and proliferation. Extensive sampling of uPAR conformational states through explicit solvent atomistic simulations followed by free energy calculations revealed that uPAR can be allosterically modulated. Based on these results we followed a multi-conformer docking approach to target alternative sites on the receptor and identify allosteric modulators of the receptor. Among the top candidates, a number of molecules were found to inhibit binding in vitro despite the distal nature of the targeted site. Finally, I describe our efforts at docking molecules to the human proteome in a multi-targeted approach to drug discovery and the creation of an online drug screening resource at http://www.biodrugscreen.org. Light refreshments to be served at 2:45 pm Host: Collin M. Stultz (cmstultz at csail.mit.edu) -------------- next part -------------- An HTML attachment was scrubbed... URL: http://mailman.mit.edu/pipermail/csbi-events/attachments/20091118/4b3c4d56/attachment.htm From csbi-events at mit.edu Fri Nov 20 12:57:40 2009 From: csbi-events at mit.edu (CSBi events) Date: Fri, 20 Nov 2009 12:57:40 -0500 Subject: [CSBi-events] TODAY at 3 PM: CSB/Biophysics Seminar - Samy Meroueh Message-ID: <000f01ca6a0a$f41e3cc0$dc5ab640$@edu> Fall 2009 Seminar Series on Computational and Systems Biology Friday, November 20, 2009 3:00 pm - 4:00 pm Room 32-463D Presenting: Computational Design of Molecules that Modulate Interactions Critical in Tumor Invasion and Metastasis Professor Samy Meroueh Department of Biochemistry and Molecular Biology and Center for Computational Biology Indiana University School of Medicine The urokinase receptor (uPAR) is a GPI-anchored cell surface receptor that focuses proteolysis at the cell surface through its association with the serine protease urokinase (uPA). In addition, uPAR activates cell surface receptors that include integrins, receptor tyrosine kinases (RTKs) and G-coupled protein receptors (GPCRs). A large body of evidence has implicated these interactions with tumor invasion and metastasis. A computational search through molecular docking is conducted to target multiple sites on uPAR in an effort to simultaneously shut down its proteolytic and signaling capabilities. A number of molecules were found to bind to the receptor as established through biochemical assays. In cell culture, compounds revealed inhibition of MDA-MB-231 breast tumor cell adhesion, migration, invasion, angiogenesis and proliferation. Extensive sampling of uPAR conformational states through explicit solvent atomistic simulations followed by free energy calculations revealed that uPAR can be allosterically modulated. Based on these results we followed a multi-conformer docking approach to target alternative sites on the receptor and identify allosteric modulators of the receptor. Among the top candidates, a number of molecules were found to inhibit binding in vitro despite the distal nature of the targeted site. Finally, I describe our efforts at docking molecules to the human proteome in a multi-targeted approach to drug discovery and the creation of an online drug screening resource at http://www.biodrugscreen.org. Light refreshments to be served at 2:45 pm Host: Collin M. Stultz (cmstultz at csail.mit.edu) -------------- next part -------------- An HTML attachment was scrubbed... URL: http://mailman.mit.edu/pipermail/csbi-events/attachments/20091120/da3c1e1a/attachment.htm