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public 01:01:13

Matt Baumgart : TBA

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public 01:34:43

Bruce Donald : Some mathematical and computational challenges arising in structural molecular biology

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Computational protein design is a transformative field with exciting prospects for advancing both basic science and translational medical research. New algorithms blend discrete and continuous mathematics to address the challenges of creating designer proteins. I will discuss recent progress in this area and some interesting open problems. I will motivate this talk by discussing how, by using continuous geometric representations within a discrete optimization framework, broadly-neutralizing anti-HIV-1 antibodies were computationally designed that are now being tested in humans - the designed antibodies are currently in eight clinical trials (See https://clinicaltrials.gov/ct2/results?cond=&term=VRC07&cntry=&state=&city=&dist= ), one of which is Phase 2a (NCT03721510). These continuous representations model the flexibility and dynamics of biological macromolecules, which are an important structural determinant of function. However, reconstruction of biomolecular dynamics from experimental observables requires the determination of a conformational probability distribution. These distributions are not fully constrained by the limited information from experiments, making the problem ill-posed in the sense of Hadamard. The ill-posed nature of the problem comes from the fact that it has no unique solution. Multiple or even an infinite number of solutions may exist. To avoid the ill-posed nature, the problem must be regularized by making (hopefully reasonable) assumptions. I will present new ways to both represent and visualize correlated inter-domain protein motions (See Figure). We use Bingham distributions, based on a quaternion fit to circular moments of a physics-based quadratic form. To find the optimal solution for the distribution, we designed an efficient, provable branch-and-bound algorithm that exploits the structure of analytical solutions to the trigonometric moment problem. Hence, continuous conformational PDFs can be determined directly from NMR measurements. The representation works especially well for multi-domain systems with broad conformational distributions. Ultimately, this method has parallels to other branches of applied mathematics that balance discrete and continuous representations, including physical geometric algorithms, robotics, computer vision, and robust optimization. I will advocate for using continuous distributions for protein modeling, and describe future work and open problems.

public 01:34:51

Bruce Pitman : CANCELLED

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CANCELLED

public 01:14:52

Ronen Plesser : G.I.T., symplectic reduction, and triangulations

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public 01:34:31

Jay Ihry : Yangians in Deformed Super Yang-Mills Theories

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public 01:29:47

Abhijit Gadde : Conformal Constraints on Defects

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public 01:00:48

Yanir Rubinstein : Einstein metrics on Kahler manifolds

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The Uniformization Theorem implies that any compact Riemann surface has a constant curvature metric. Kahler-Einstein (KE) metrics are a natural generalization of such metrics, and the search for them has a long and rich history, going back to Schouten, Kahler (30's), Calabi (50's), Aubin, Yau (70's) and Tian (90's), among others. Yet, despite much progress, a complete picture is available only in complex dimension 2. In contrast to such smooth KE metrics, in the mid 90's Tian conjectured the existence of KE metrics with conical singularities along a divisor (i.e., for which the manifold is `bent' at some angle along a complex hypersurface), motivated by applications to algebraic geometry and Calabi-Yau manifolds. More recently, Donaldson suggested a program for constructing smooth KE metrics of positive curvature out of such singular ones, and put forward several influential conjectures. In this talk I will try to give an introduction to Kahler-Einstein geometry and briefly describe some recent work mostly joint with R. Mazzeo that resolves some of these conjectures. One key ingredient is a new C^{2,\alpha} a priori estimate and continuity method for the complex Monge-Ampere equation. It follows that many algebraic varieties that may not admit smooth KE metrics (e.g., Fano or minimal varieties) nevertheless admit KE metrics bent along a simple normal crossing divisor.