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ACS Computers in Chemistry Awards :
02:00pm - 05:40pm USA / Canada - Pacific - March 21, 2022 | Location: Room 24C (San Diego Convention Center)
Adrian Roitberg, Organizer, Presider; Carlos Simmerling, Organizer, Presider; Karl Kirschner, Organizer, Presider
Division: [COMP] Division of Computers in Chemistry
Session Type: Oral - In-person
Division/Committee: [COMP] Division of Computers in Chemistry
Monday
Introduction
02:00pm - 02:10pm USA / Canada - Pacific - March 21, 2022 | Location: Room 24C (San Diego Convention Center)
Division: [COMP] Division of Computers in Chemistry
Session Type: Oral - In-person

Monday
3678832 - Role of small mechanical forces in the function of proteins
02:10pm - 02:40pm USA / Canada - Pacific - March 21, 2022 | Location: Room 24C (San Diego Convention Center)
Glen Hocky, Presenter
Division: [COMP] Division of Computers in Chemistry
Session Type: Oral - In-person

Proteins and other biomolecules in cells are constantly subjected to mechanical forces that cause them to be compressed or extended. These are due to passive thermal fluctuations as well as “active” processes with in the cell which consume molecules to produce mechanical work. Here I will discuss how these forces shape the conformational landscape of proteins, and in particular, roles that mechanical forces play in the context of the actin cytoskeleton. The actin cytoskeleton is an active mechanical gel within cells made up of non- covalent polymers of the protein actin, crosslinkers, and molecular motors. We will explore the multiscale nature of this system, where protein conformation and response to mechanical forces has an emergent large-scale effect on the macroscopic mechanical properties of the system.

Monday
3678826 - Photodynamics simulations explain photochemical reactivity and selectivities towards strained molecules
02:40pm - 03:10pm USA / Canada - Pacific - March 21, 2022 | Location: Room 24C (San Diego Convention Center)
Steven Lopez, Presenter
Division: [COMP] Division of Computers in Chemistry
Session Type: Oral - 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.
Monday
Intermission
03:10pm - 03:25pm USA / Canada - Pacific - March 21, 2022 | Location: Room 24C (San Diego Convention Center)
Division: [COMP] Division of Computers in Chemistry
Session Type: Oral - In-person

Monday
3678821 - Establishing the allosteric mechanism in CRISPR-Cas9
03:25pm - 03:55pm USA / Canada - Pacific - March 21, 2022 | Location: Room 24C (San Diego Convention Center)
Giulia Palermo, Presenter
Division: [COMP] Division of Computers in Chemistry
Session Type: Oral - In-person

Allostery is a fundamental property of the CRISPR-Cas9 molecular machinery, which regulates biochemical information transfer between spatially distant sites. Here, we report the application of computational methods to describe the signal transfer, connecting DNA recognition to cleavage, in the Cas9 protein. By using advanced network theory, we described CRISPR-Cas9 as a network of nodes and edges to quantify the signal transduction between the HNH and RuvC nucleases. Similar to social media analysis, our methods enabled identification of the “hubs” in the protein network that are major players in the information transfer. We described how allostery intervenes during at least three steps of the CRISPR-Cas9 function: affecting DNA recognition, mediating the cleavage and interfering with the off-target activity. At first, we found that PAM binding acts as an allosteric activator, triggering concerted motions (and cleavages) of the spatially distant HNH and RuvC. As also supported by structural studies, the allosteric communication between HNH and RuvC flows through the L1/L2 interconnecting loops, which act as “allosteric transducers”. Inspired by single molecule studies, computational models also described the critical role of the REC3 region in modulating the dynamics and the catalytic activity of HNH. The role of REC3 was revealed to be particularly relevant in the presence of DNA mismatches. Indeed, interference of REC3 with the RNA:DNA hybrid containing mismatched pairs at specific positions resulted in locking HNH in an inactive “conformational checkpoint”, thereby hampering off-target cleavages. In line with our studies, engineering of the allosteric sites has shown to improve the system’s specificity, thereby paving the way for controlling the CRISPR-Cas9 activity though the modulation of its allosteric function. Taken together, computational methods contributed in establishing the fundamental mechanisms underlying the allosterism of CRISPR-Cas9, aiding engineering strategies to develop new Cas9 variants for improved genome editing.

Monday
3678828 - CASPT2 molecular geometries for Fe(II) spin-crossover complexes
03:55pm - 04:25pm USA / Canada - Pacific - March 21, 2022 | Location: Room 24C (San Diego Convention Center)
Division: [COMP] Division of Computers in Chemistry
Session Type: Oral - In-person
Using fully internally contracted (FIC)-CASPT2 analytical gradients, geometry optimizations of spin-crossover complexes are reported. This approach is tested on a series of Fe(II) complexes with different sizes, ranging from 13 to 61 atoms. A combination of active space and basis set choices are employed to investigate their role in determining reliable molecular geometries. The reported strategy demonstrates that a wave function-based level of theory can be used to optimize the geometries of metal complexes in reasonable times and enables one to treat the molecular geometry and electronic structure of the complexes using the same level of theory. For a series of smaller Fe(II) SCO complexes, strong field ligands in the LS state result in geometries with the largest differences between DFT and CASPT2; however, good agreement overall is observed between DFT and CASPT2. For the larger complexes, moderate sized basis sets yield geometries that compare well with DFT and available experimental data. We recommend using the (10e,12o) active space since convergence to a minimum structure was more efficient than with truncated active spaces (e.g., (6e,5o)) despite having similar Fe–ligand bond distances.
Monday
Intermission
04:25pm - 04:40pm USA / Canada - Pacific - March 21, 2022 | Location: Room 24C (San Diego Convention Center)
Division: [COMP] Division of Computers in Chemistry
Session Type: Oral - In-person

Monday
Early/Mid-Career Panel
04:40pm - 05:40pm USA / Canada - Pacific - March 21, 2022 | Location: Room 24C (San Diego Convention Center)
Division: [COMP] Division of Computers in Chemistry
Session Type: Oral - In-person