Session Type Key

Hybrid Sessions
Virtual Sessions
In-Person Sessions

custom image


Reset

Advanced Filters

OpenEye Outstanding Junior Faculty Award:
07:00pm - 09:00pm USA / Canada - Pacific - March 22, 2022 | Location: Exhibit Hall C (San Diego Convention Center)
Adrian Roitberg, Organizer; Carlos Simmerling, Organizer
Division: [COMP] Division of Computers in Chemistry
Session Type: Poster - In-person
Division/Committee: [COMP] Division of Computers in Chemistry
Tuesday
3644889 - Harnessing enhanced sampling molecular dynamics techniques to predict the response of biomolecules to piconewton-scale mechanical forces
07:00pm - 09:00pm USA / Canada - Pacific - March 22, 2022 | Location: Exhibit Hall C (San Diego Convention Center)
Glen Hocky, Presenter
Division: [COMP] Division of Computers in Chemistry
Session Type: Poster - In-person
Our goal is to predict the response of biomolecules to the small, thermal scale, mechanical forces they experience within cells. Active processes in biological systems such as the motion of molecular motors produce piconewton-scale mechanical forces on supramolecular assemblies, and many proteins have evolved to sense and respond to these forces. Yet these forces are very small, and we would not expect them to have a large effect on a protein’s conformation or conformational ensemble. Hence, robustly predicting the response of these mechanosensors at the molecular level is a challenge. Here, I present our efforts to develop enhanced sampling protocols that can allow us to make testable predictions about molecular mechanosensing mechanisms. Our efforts are broadly divided into two areas: predicting the change in conformational ensemble at constant force at equilibrium, for which we have developed an efficient force tempering method known as FISST, and predicting the dissociation rate of protein-protein complexes under force, for which we are employing infrequent metadynamics and weighted ensemble approaches. I will present both our methodological work on test systems as well as application to real mechanosensing proteins, including peptide tension sensors, cytoskeletal protein complexes, and bacterial membrane channels.
Tuesday
3646126 - Photodynamics simulations explain photochemical reactivity and selectivities towards strained molecules
07:00pm - 09:00pm USA / Canada - Pacific - March 22, 2022 | Location: Exhibit Hall C (San Diego Convention Center)
Steven Lopez, Presenter
Division: [COMP] Division of Computers in Chemistry
Session Type: Poster - In-person
Photochemical reactions are increasingly important for the construction of value-added, strained organic architectures. Direct excitation and photoredox reactions typically require mild conditions and permit access highly strained molecules and new synthetic methodologies. The a priori design of photochemical reactions is challenging because degenerate excited states often result in competing reaction mechanisms to undesired products. Further, a lack of experimental techniques that provide atomistic structural information on ultrafast timescales (10–15 – 10–12 s) limits general ‘chemical intuition’ about these processes. Computations, however, provide a path forward. I will discuss how my group has leveraged state-of-the-art quantum mechanical calculations, non-adiabatic molecular dynamics, and machine learning (ML) techniques to understand the reactivities and selectivities of a photochemical cascade reaction towards the first stable polyacetylene, fluoropolyacetylene. I will introduce our new open-access machine learning tool, Python Rapid Artificial Intelligence Ab Initio Molecular Dynamics (PyRAI2MD), which enables 1,000-fold longer simulations than are currently possible with multiconfigurational NAMD simulations. PyRAI2MD has enabled nanosecond ML-NAMD simulations on stereoselective electrocyclic reactions with record degrees of freedom and molecular complexities.
Tuesday
3646136 - Multiscaling the CRISPR-Cas revolution from gene editing to viral detection
07:00pm - 09:00pm USA / Canada - Pacific - March 22, 2022 | Location: Exhibit Hall C (San Diego Convention Center)
Giulia Palermo, Presenter
Division: [COMP] Division of Computers in Chemistry
Session Type: Poster - In-person
CRISPR is synonymous with a transformative genome editing technology that is innovating basic and applied sciences. I will report about the use of computational approaches to clarify the molecular basis and the gene-editing function of CRISPR-Cas9 and newly discovered CRISPR systems that are emerging as powerful tools for viral detection, including the SARS-CoV-2 coronavirus. We have implemented a multiscale approach, which combines classical molecular dynamics (MD) and enhanced sampling techniques, ab-initio MD, mixed Quantum Mechanics/Molecular Mechanics (QM/MM) approaches and constant pH MD (CpH MD), as well as cryo-EM fitting tools and graph theory derived analysis methods, to reveal the mechanistic basis of nucleic acid binding, catalysis, selectivity, and allostery in CRISPR systems. Using a Gaussian accelerated MD method and the Anton-2 supercluster we determined the conformational activation of CRISPR-Cas9 and the selectivity mechanism against off-target sequences. By applying network models graph theory, we have characterized a mechanism of allosteric regulation, transferring the information of DNA binding to the catalytic sites for cleavages. This mechanism is now being probed in novel Anti-CRISPR proteins, forming multi-mega Dalton complexes with the CRISPR enzymes and used for gene regulation and control. CpH MD simulations have been combined with ab-initio MD and a mixed QM/MM approach to establish the catalytic mechanism of DNA cleavage. Finally, by using multi-microsecond MD simulations we have recently probed a mechanism of DNA-induced of activation in the Cas12a enzyme, which underlies the detection of viral genetic elements, including the SARS-CoV-2 coronavirus. Overall, our outcomes contribute to the mechanistic understanding of CRISPR-based gene-editing technologies, providing information that is critical for the development of improved gene-editing tools for biomedical applications.

Tuesday
3646560 - CASPT2 molecular geometries for transition metal complexes
07:00pm - 09:00pm USA / Canada - Pacific - March 22, 2022 | Location: Exhibit Hall C (San Diego Convention Center)
Division: [COMP] Division of Computers in Chemistry
Session Type: Poster - In-person
The optimization of molecular geometries for systems with multiconfigurational electronic structures can be performed using the recently implemented fully internally contracted analytical gradients for the second-order complete active space SCF method (CASPT2). We demonstrate the performance of this method for two types of complexes. The first family of complexes explored present a characteristic geometry change for systems ranging in size from 13 to 61 atoms. Specifically, the metal ligand bond distance in Fe(II) spin-crossover complexes is elongated in the high spin state compared to the low spin state. The quality of the optimized geometry and its impact on the relative energies of the high spin and low spin state are assessed. Next, we move beyond geometry optimizations and study the vibrational spectroscopy of chromium-chromium metal-metal bonds which present prototypical examples of multiconfigurational electronic structures. We explore three complexes and show that good geometries can be obtained, although the choice of CASPT2 zeroth-order Hamiltonian is important. We also calculate the Raman active metal-metal and metal-ligand stretching modes, making comparisons with isotope labeling experiments. The effect of anharmonicity is also explored by normal mode sampling. Comparisons with density functional theory are made in all cases.