Greater Boston Area Theoretical Chemistry Lecture Series

2018-2019 Speaker Schedule

Enhanced Sampling methods for studying and designing cyclic peptides

09/19/18 4:15pm

MIT Building 4, Room 237

Yu-Shan Lin

Tufts University, Boston




Yu-Shan Lin

Protein–protein interactions (PPIs) play critical roles in many important and disease-relevant biological processes. Modulating PPIs thus provides a means to control diverse cellular functions for both fundamental research and therapeutic intervention. Unfortunately, protein–protein interfaces are challenging targets for traditional small molecules because the interfaces are relatively large and flat. Cyclic peptides (CPs) offer a promising solution for targeting PPIs, owing to their inherently large surface area and their ability to easily mimic functional groups and structures at protein interfaces. However, the high potential applicability of CPs is currently severely limited by our poor capacity to accurately predict CP structures. We recently developed an enhanced sampling method that uses metadynamics to target the coupled two-dihedral motions during conformational switches of cyclic peptides. This technique enables efficient simulations of CPs using even all-atom force fields and explicit solvent models and thus allows more accurate description of CP structures and energetics to be used during their rational design. In this talk, we describe how we used MD simulations and enhanced sampling methods to achieve the first accurate de novo structure prediction of cyclic penta- and hexapeptides, and our current progress in developing a platform for designing CPs to target PPIs.

Fragment-based Quantum Chemical Methods for Calculating Accurate Energies and Properties of Large Molecules and Nanoscale Systems

09/26/18 4:15pm

MIT Building 4, Room 237

Krishnan Raghavachari

Indiana University Bloomington




Krishnan Raghavachari

The development of accurate and broadly applicable models for large molecules is a major challenge in quantum chemistry. We are presently developing a hierarchy of novel fragment-based methods for the accurate description of the electronic structures and properties of large molecules. The electronic energies, molecular geometries, reactive potential energy surfaces, and many spectroscopic properties of a variety of large molecules have been investigated by our new methods. Our methods are also beginning to find applications in problems involving computer-aided design of receptors and drug molecules. We will describe the key ideas behind our Molecules-in-Molecules (MIM) fragment-based method, and present results from novel applications on a range of large molecules and nanoscale systems.

Insights into Complex Molecular Processes from Quantitative Atomistic Simulations

10/24/18 4:15pm

MIT Building 4, Room 237

Markus Meuwly

University of Basel




Markus Meuwly

Molecular dynamics simulations are a powerful means to provide molecular-level insights into processes ranging from gas-phase reaction dynamics to complex non-reactive and reactive rearrangements in biological systems. The utility of such simulations depends sensitively on the accuracy with which the intermolecular interactions are represented. In this seminar I will discuss recent progress in force field development including multipolar force fields, reproducing kernel Hilbert space techniques and machine learning and their application to spectroscopy and reactive processes in the condensed phase. The focus is on directly linking experimental observations with computations which provides molecular level understanding of spectroscopic observables and time scales from state-of-the art experiments. A typical example will be the relationship between structure and dynamics for infrared and X-ray absorption spectroscopy of biomolecules or the thermodynamics of reversed phase liquid chromatography.

Molecular simulations of lipid membrane sensing and shaping

11/14/18 4:15pm

MIT Building 4, Room 237

Gerhard Hummer

Max Planck Institute of Biophysics, Germany




Gerhard Hummer

Living cells need to exert tight control over their lipid membranes to maintain their internal structure, to guard their outside boundary, to establish potential and concentration gradients as their energy source, and to transmit signals between their compartments and to the outside. As a consequence, elaborate machineries have evolved that allow cells to sense and regulate the composition, shape and physical characteristics of their lipid membranes. In my talk I will give an overview of the physics and chemistry used by these machineries, as identified by molecular dynamics simulations combined with experiments.

11/28/18 4:15pm

MIT Building 4, Room 237

Jianzhi George Zhang

University of Michigan




Jianzhi George Zhang

Part 1. What determines the rate of protein sequence evolution and why The rate and mechanism of protein sequence evolution have been central questions in evolutionary biology since the 1960s. Although the rate of protein sequence evolution depends primarily on the level of functional constraint, exactly what determines the functional constraint has remained unclear. The increasing availability of genomic data has enabled much needed empirical examinations on the nature of functional constraint. These studies found that the evolutionary rate of a protein is predominantly influenced by its expression level rather than functional importance. A combination of theoretical and empirical analyses has identified multiple mechanisms behind these observations and demonstrated a prominent role in protein evolution of selection against errors in molecular and cellular processes. Part 2. Multi-environment fitness landscapes of a yeast tRNA gene Fitness landscapes describe genotype-fitness relationships and are important for explaining and predicting evolution. But fitness landscapes are hard to map due to the sheer size of the genotype space coupled with the difficulty in accurately measuring fitness. In this talk, I describe our development of a high-throughput method for mapping fitness landscapes. We used this method to quantify the fitness in multiple environments for tens of thousands of yeast strains, each carrying a unique variant of a tRNA gene at its native genomic location. The obtained data allowed us to study the mechanistic basis of fitness landscapes and probe the impact of the environment on mutational effects. Some simple rules appear to underlie seemingly complex fitness landscapes.

Photoinduced processes in biosystems: a multiscale strategy to go from understanding to manipulation

01/30/19 4:15pm

MIT Building 32, Room 144

Benedetta Mennucci

University of Pisa, Italy




Benedetta Mennucci

Organisms of all domains of life are capable of sensing, using and responding to light. The molecular mechanisms used are diverse, but most commonly the starting event is the light absorption by a (multi)chromophoric unit embedded in the biomatrix. The key issue is exactly the composite embedding matrix (the protein, the membrane, the solvent) which can control and regulate the photoinduced process through an interplay of different interactions and dynamical effects. In this talk, I’ll present and discuss a multiscale computational strategy which integrates quantum chemistry, classical models and molecular dynamics simulations to investigate photoinduced processes in pigment-protein complexes and propose their manipulation through the design of biohybrid systems.

Molecular simulation tools for investigating structure and dynamics of intrinsically disordered proteins

02/13/19 4:15pm

MIT Building 4, Room 231

Robert Best

NIH




Robert Best

Intrinsically disordered proteins (IDPs) are increasingly realized to play a wide range of functional as well as pathological roles in biology. However, biophysical characterization of these proteins is experimentally challenging due to the extremely heterogeneous ensemble of structures which they populate. Computational tools, in particular molecular simulations, can therefore play a role in elucidating structure, function and dynamics in IDPs. Here, I will show how both detailed atomistic simulations, as well as simplified coarse-grained models can be used to assist in the interpretation of experiments on IDPs, although in each case careful parameterization is essential. I will discuss how the simulation results can be related to the available experimental measurements, and how they can be integrated with experimental data in order to obtain the most accurate picture of the conformational ensemble. I will discuss the application of these methods to resolving an apparent contradiction between the results of different experiments on disordered proteins, to characterizing an ultra-high affinity complex between two charged IDPs which, remarkably, remain completely disordered upon binding, and to advancing our understanding of liquid-liquid phase separation which drives the formation of so-called membraneless organelles.

The Mysteries of Chirality, Solvation, and Optical Activity

02/20/19 4:15pm

MIT Building 4, Room 231

Daniel Crawford

Virginia Tech




Daniel Crawford

The optical properties of chiral molecules are among the most challenging to predict and simulate — even for state-of-the-art quantum chemical methods — because of their delicate dependence on a variety of intrinsic and extrinsic factors, including electron correlation, basis set, vibrational/temperature effects, etc. In numerous studies over the last decade, we have demonstrated the importance of advanced quantum chemical methods such as coupled cluster response theory for the prediction of an array of gas-phase chiroptical properties such as optical rotation angles, circular dichroism rotatory strengths, Raman optical activity scattering intensity differences, and more. The primary disadvantage of such methods, however, is their high-degree polynomial scaling, which limits significantly the size of system to which they may be applied. Furthermore, solvation makes the task even more difficult, not only dramatically expanding the complexity of the simulation, but sometimes altering even the sign of the chiral response. It is thus essential that we reduce the computational demands of the more accurate and reliable quantum chemical methods. This lecture will explore the many ways in which we are pursuing both more efficient theoretical models of optical activity, but means for extracting deeper understanding from them.

Electronically Excited States and Transition-Metal Containing Systems are a Challenge for Modern Quantum Chemistry

02/26/19 4:15pm (TUESDAY)

MIT Building 4, Room 163

Laura Gagliardi

University of Minnesota




Laura Gagliardi

I will report our latest developments of multireference methods with special focus on multiconfiguration pair-density functional theory (MC-PDFT) and its application to understanding the properties and reactivity of electronically excited states and transition metal-containing systems. MC-PDFT combines mutireference wave functions and density functional theory methods to treat strongly correlated systems. I will illustrate examples of multireference systems, including supported hetero-bimetallic clusters and their properties as catalysts and describe the challenges in modeling them. Finally I will describe our latest effort in developing embedding methods for strongly correlated systems.

postponed

03/06/19 4:15pm

MIT Building 4, Room 231

Dan Tawfik

Weizmann Institute of Science




Dan Tawfik

postponed

Computational and experimental studies of epistasis in proteins

03/20/19 4:15pm

MIT Building 4, Room 231

Mike Harms

University of Oregon




Mike Harms

The Harms lab is interested in the intersection of protein biophysics and protein evolution. One area of interest is the ubiquitous phenomenon of epistasis, where the effect of a mutation changes when other mutations are introduced. Epistasis profoundly shapes evolutionary rates, allows for the assembly of multi-mutation protein features, and introduces profound contingency into the evolutionary process. Epistasis also provides information that can be used to dissect the underlying biochemistry of proteins. In my talk, I will discuss the historical context for studies of epistasis, biochemical mechanisms that cause it, and the consequences of epistasis for protein evolution. I will also discuss some of the computational and experimental work from my lab in which we attempt to understand the molecular underpinnings of epistasis, with a specific focus on high-order interactions involving three or more mutations.

Physical Basis of Protein Liquid-Liquid Phase Separation

03/27/19 4:15pm

MIT Building 4, Room 231

Huan-Xiang Zhou

University of Illinois at Chicago




Huan-Xiang Zhou

Intracellular membraneless organelles, corresponding to the droplet phase upon liquid-liquidphase separation (LLPS) of mixtures of proteins and possibly RNA, mediate myriad cellularfunctions. Cells use a variety of biochemical signals such as expression level andposttranslational modification to regulate droplet formation and dissolution. Our study focuseson elucidating the physical basis of phase behaviors associated with cellular functions of membraneless organelles, usingfourcomplementary approaches. First, we use colloids and polymers, respectively, as models for structured and disordered proteins, to investigate both the common basis for protein phase separation and the unique characteristics of structured and disordered proteins in LLPS. Disordered proteins are characterized by both extensive intermolecular attraction and low excluded-volume entropy, contributing to ready observation of phase separation. Second, we use multi-component patchy particles to investigate the wide range of effects of regulatory components on the droplet formation of driver proteins. Third, the theoretical predictions have motivated our experimental work to define archetypical classes of macromolecular regulators of LLPS. Lastly, we have developed a powerful computational method called FMAP for determining liquid-liquid phase equilibria. By using fast Fourier transform to efficiently evaluate protein-protein interactions, FMAP enables an atomistic representation of the protein molecules. Application to -crystalins reveals how minor variations in amino-acid sequence, similar to those from post translational modifications and disease-associated mutations, lead to drastic differences in critical temperature. These studies contribute to both qualitative and quantitative understanding on the phase behaviors of membraneless organelles and their regulation and dysregulation.

Polymers in Ionic Liquids

04/10/19 4:15pm

MIT Building 4, Room 231

Arun Yethiraj

University of Wisconsin-Madison




Arun Yethiraj

Ionic liquids have generated considerable excitement for their varied potential applications and their interesting physical properties. The viability of ionic liquids (ILs) in materials applications is limited by their lack of mechanical integrity, which may be provided by mixing them with a polymeric material. Recent experiments on polymers in ILs have unearthed a wealth of interesting phenomena that raise fundamental questions. This talk focuses on computational studies of PEO in imidazolium ILs. We develop a physically motivated first principles force field for PEO and [BMIM] [BF4]; this force field is in quantitative agreement with experiment with no adjustable parameters. Based on the same quantum calculations we develop a hierarchy of united atom models with decreasing resolution and increasing computational efficiency. Microsecond simulations are required to obtain converged properties of the polymer, which displays a combination of ring-like and extended conformations. The simulations show the existence of a lower critical solution temperature which arises from conformational restrictions on the polymer molecules at low temperatures.

New Theoretical Approaches to Investigate Reactions Enabled by Quantum Mechanical Behavior

05/01/19 4:15pm

MIT Building 4, Room 231

Pengfei Frank Huo

University of Rochester




Frank Huo

A central research theme in my group is developing new theoretical approaches to investigate chemical reactivities when they are enabled by intrinsically quantum mechanical behavior. These quantum behaviors, such as strong couplings between molecules and quantized photons have the potential to facilitate new chemical reactivities and enable new paradigms for chemical transformations. Understanding the real-time dynamics of these processes will inspire design principles that take advantage of intrinsic quantum behaviors. In this talk, I will discuss our recent efforts to explore new chemical reactivities enabled by polaritons, a set of photon-matter hybrid states generated by quantum light-matter interactions. Further, I will discuss two approaches that we developed for accurate and efficient quantum dynamics simulations: (i) the quasi-diabatic (QD) propagation scheme which enables a seamless interface between an accurate diabatic quantum dynamics approach and any routinely available adiabatic electronic structure method, (ii) coherent state ring polymer molecular dynamics method that accurately treats electronic non-adiabatic transitions and nuclear quantum effects through a consistent, classical-like treatment of all degrees of freedom.

Protein Conformational Changes and Ligand Binding

05/08/19 4:15pm

MIT Building 4, Room 231

Andy McCammon

UC San Diego




Andy McCammon

Protein Conformational Changes and Ligand Binding: Thermodynamics Protein Conformational Changes and Ligand Binding: Kinetics

The Nanoporous Materials Genome in Action

05/13/19 4:15pm

MIT Building 4, Room 231

Berend Smit

UC Berkeley




Berend Smit

The attractive feature of Metal Organic Frameworks (MOFs) is that practical limitations we can only ever synthesize, characterize, and test a tiny fraction of all possible materials. To take full advantage of this development, therefore, we need to develop alternative techniques, collectively referred to as Materials Genomics [1], to rapidly screen large numbers of materials and obtain fundamental insights into the chemical nature of the ideal material for a given application. These computational materials genomics initiatives have been so successful that we have created a new problem: what to do with so much data? In this presentation we will discuss different computational strategies to deal with a large amount of data. We illustrate on the use of these strategies by addressing the following questions: How the find the best material for a given application? How to find materials with similar pore shape [2]? How to design a material that optimally binds CO2? And, what can we learn from failed experiments?[3] [1] P. G. Boyd, Y. Lee, and B. Smit, Computational development of the nanoporous materials genome Nat. Rev. Mater. 2, 17037 (2017) [2] Y. Lee, S. D. Barthel, P. Dlotko, S. M. Moosavi, K. Hess, and B. Smit, Quantifying similarity of pore-geometry in nanoporous materials Nat. Commun. 8, 15396 (2017) [3] S. M. Moosavi, A. Chidambaram, L. Talirz, M. Haranczyk, K. C. Stylianou, and B. Smit, Capturing chemical intuition in synthesis of metal-organic frameworks Nat. Commun. 10 (2019)

Past Schedules