@article{torkelson_pfaendtner_2024, title={Exploration of Tertiary Structure in Sequence-Defined Polymers Using Molecular Dynamics Simulations}, volume={9}, ISSN={["1526-4602"]}, DOI={10.1021/acs.biomac.4c00527}, abstractNote={Peptoids are a class of sequence-defined biomimetic polymers with peptide-like backbones and side chains located on backbone nitrogens rather than alpha carbons. These materials demonstrate a strong ability for precise control of single-chain structure, multiunit self-assembly, and macromolecular assembly through careful tuning of sequence due to the diversity of available side chains, although the driving forces behind these assemblies are often not understood. Prior experimental work has shown that linked 15mer peptoids can mimic the protein helical hairpin structure by leveraging the chirality-inducing nature of bulky side chains and hydrophobicity, but there are still gaps in our understanding of the relationship between sequence, stability, and particular secondary or tertiary structure. We present a molecular dynamics (MD) study on the folding behavior of these polymers into hairpins, discussing the differences in structure from sequences with various characteristics in water and acetonitrile, and then compare the handedness preference of common helical motifs between solvents.}, journal={BIOMACROMOLECULES}, author={Torkelson, Kaylyn and Pfaendtner, Jim}, year={2024}, month={Sep} }
 @article{qi_pfaendtner_2024, title={High-Throughput Computational Screening of Solid-Binding Peptides}, volume={3}, ISSN={["1549-9626"]}, DOI={10.1021/acs.jctc.3c01286}, abstractNote={Inspired by biomineralization, a naturally occurring, protein-facilitated process, solid-binding peptides (SBPs) have gained much attention for their potential to fabricate various shaped nanocrystals and hierarchical nanostructures. The advantage of SBPs over other traditionally used synthetic polymers or short ligands is their tunable interaction with the solid material surface via carefully programmed sequence and being solution-dependent simultaneously. However, designing a sequence with targeted binding affinity or selectivity often involves intensive processes such as phage display, and only a limited number of sequences can be identified. Other computational efforts have also been introduced, but the validation process remains prohibitively expensive once a suitable sequence has been identified. In this paper, we present a new model to rapidly estimate the binding free energy of any given sequence to a solid surface. We show how the overall binding of a polypeptide can be estimated from the free energy contribution of each residue based on the statistics of the thermodynamically stable structure ensemble. We validated our model using five silica-binding peptides of different binding affinities and lengths and showed that the model is accurate and robust across a wider range of chemistries and binding strengths. The computational cost of this method can be as low as 3% of the commonly used enhanced sampling scheme for similar studies and has a great potential to be used in high-throughput algorithms to obtain larger training data sets for machine learning SBP screening.}, journal={JOURNAL OF CHEMICAL THEORY AND COMPUTATION}, author={Qi, Xin and Pfaendtner, Jim}, year={2024}, month={Mar} }
 @article{waggett_pfaendtner_2024, title={Hydrophobic Residues Promote Interfacial Activation of <i>Candida rugosa</i> Lipase: A Study of Rotational Dynamics}, volume={8}, ISSN={["1520-5827"]}, DOI={10.1021/acs.langmuir.4c02174}, abstractNote={Microbial lipases constitute a class of biocatalysts with the ability to cleave ester linkages of long-chain triglycerides. This property makes them particularly attractive for industrial applications ranging from food processing to pharmaceutical preparation. Among such enzymes, Candida rugosa lipase (CRL) is one of the most frequently used in biotransformation. A notable feature of CRL, among many lipases, is its propensity for interfacial activation: these enzymes exhibit elevated catalytic rates when acting at the interface between aqueous and hydrophobic phases. Notably, this phenomenon can be attributed to the presence of a mobile lid domain, which in its closed state occludes the enzyme active site. To advance our understanding of interfacial activation, we explore the dynamics of CRL rotation at the octane–water interface in this work. To do so, we employ molecular dynamics and umbrella sampling to evaluate the free energy of rotation of the enzyme at the interface. We identify a global minimum in the rotational landscape that coincides with lid opening at the interface. Additionally, we investigate the role of surface residues outside the lid domain as they serve to instigate rotation of the lid toward the aqueous phase. In doing so, we identify a patch of leucine residues which when mutated to glycine impose a barrier to rotation that maintains the enzyme in the inactive (closed lid) state on the order of 1 μs. Importantly, this study presents a novel quantification of the rotational free energy corresponding to CRL lid opening at the octane–water interface. The accompanying mutagenesis study likewise clarifies the role of hydrophobic surface residues in the transition. As such, this work provides valuable insight into the phenomenon of interfacial activation that might open up new avenues for manipulating the microenvironment of industrially relevant lipases, affording enhanced control over the enzyme state.}, journal={LANGMUIR}, author={Waggett, Ava and Pfaendtner, Jim}, year={2024}, month={Aug} }
 @article{mao_sampath_pfaendtner_2024, title={Molecular Driving Forces in the Self-Association of Silaffin Peptide R5 from MD Simulations}, volume={5}, ISSN={["1439-7633"]}, DOI={10.1002/cbic.202300788}, abstractNote={The 19-residue silaffin-R5 peptide has been widely studied for its ability to precipitate uniform SiO}, journal={CHEMBIOCHEM}, author={Mao, Coco M. and Sampath, Janani and Pfaendtner, Jim}, year={2024}, month={May} }
 @article{torkelson_naser_qi_li_yang_pushpavanam_chen_baneyx_pfaendtner_2024, title={Rational Design of Novel Biomimetic Sequence-Defined Polymers for Mineralization Applications}, volume={36}, ISSN={["1520-5002"]}, DOI={10.1021/acs.chemmater.3c02216}, abstractNote={Silica biomineralization is a naturally occurring process, wherein organisms use proteins and other biological structures to direct the formation of complex, hierarchical nanostructures. Discovery and characterization of such proteins and their underlying mechanisms spurred significant efforts to identify routes for biomimetic mineralization that reproduce the exquisite shapes and size selectivities found in nature. A common strategy has been the use of short peptide sequences with chemistry mimicking those found in natural systems, such as the use of the silaffin-derived R5 peptide. While progress has been made using this approach, there are many limitations that have prevented breakthroughs in biomimicry. To advance our ability to use charged macromolecules for silica formation, we propose to use sequence-defined synthetic polymers known as peptoids, or N-substituted polyglycines, which present significant capability for the precise tuning of sequence and structure beyond what can often be achieved with peptides alone. This study presents a computationally predicted design of these polymers that leads to the controlled formation of silica nanomaterials. We investigate surface adsorption and the mineralization process through analysis of binding mechanisms and energetics of the R5 system. Next, we synthesized two R5-inspired peptoids and validated our prediction in the design of mineralization polymers through characterization using surface plasmon resonance and electron microscopy. This computationally guided study holds great promise for designing new sequences with unprecedented control of the placement of chemical functional groups, thus allowing for further unraveling of silicification mechanisms and the eventual design of sequence-defined synthetic polymers leading to the predictive synthesis of nanostructured functional materials.}, number={2}, journal={CHEMISTRY OF MATERIALS}, author={Torkelson, Kaylyn and Naser, Nada Y. and Qi, Xin and Li, Zhiliang and Yang, Wenchao and Pushpavanam, Karthik and Chen, Chun-Long and Baneyx, Francois and Pfaendtner, Jim}, year={2024}, month={Jan}, pages={786–794} }
 @article{sanghavi_intan_xie_lin_pfaendtner_2024, title={Reaction Pathway Analysis of PET Deconstruction via Methanolysis and Tertiary Amine Catalysts}, volume={128}, ISSN={["1520-5215"]}, DOI={10.1021/acs.jpca.4c02276}, abstractNote={Polyethylene terephthalate (PET) is a type of polymer frequently used in plastic packaging that significantly adds the amount of plastic waste found in landfills. One of the ways to recover valuable raw materials from postconsumer plastic is by depolymerizing PET into its monomeric constituents, which are dimethyl terephthalate (DMT) and ethylene glycol. PET depolymerization is often done in methanolysis with the help of acidic or base catalysts. Tertiary amine is one of the most attractive base catalysts for PET depolymerization in methanolysis since it does not lead to the generation of potentially environmentally harmful waste, unlike metal-based catalysts. However, the mechanism by which tertiary amines catalyze PET depolymerization in methanolysis remains unexplored. Developing a detailed mechanistic understanding of this process is important for improving plastic upcycling since it opens the possibility of employing various cheaper and more environmentally friendly reaction conditions. Using density functional theory and transition state analysis, we show that in the presence of tertiary amine catalysts, methanolysis of PET consists of multiple discrete-step reactions rather than a single concerted step. Furthermore, by comparing our calculations to recent experimental results, we were able to rationalize the DMT yield from the depolymerization process by relating it to charge polarization within tertiary amine catalysts, thus opening a pathway to identify atomic descriptors for future catalyst design.}, number={29}, journal={JOURNAL OF PHYSICAL CHEMISTRY A}, author={Sanghavi, Rishabh and Intan, Nadia N. and Xie, Shaoqu and Lin, Hongfei and Pfaendtner, Jim}, year={2024}, month={Jul}, pages={5883–5891} }
 @article{zorman_phillips_shi_zhang_de yoreo_pfaendtner_2024, title={Thermodynamic Analysis of Silk Fibroin-Graphite Hybrid Materials and Their Morphology}, volume={2}, ISSN={["1520-5207"]}, DOI={10.1021/acs.jpcb.3c08147}, abstractNote={Silk fibroin (SF) is a β-sheet-rich protein that is responsible for the remarkable tensile strength of silk. In addition to its mechanical properties, SF is biocompatible and biodegradable, making it an attractive candidate for use in biotic/abiotic hybrid materials. A pairing of particular interest is the use of SF with graphene-based nanomaterials (GBNs). The properties of this interface drive the formation of well-ordered nanostructures and can improve the electronic properties of the resulting hybrid. It was previously demonstrated that SF can form lamellar nanostructures in the presence of graphite; however, the equilibrium morphology and associated driving interactions are not fully understood. In this study, we characterize these interactions between SF and SF lamellar with graphite using molecular dynamics (MD) simulations and umbrella sampling (US). We find that SF lamellar nanostructures have strong orientational and spatial preferences on graphite that are driven by the hydrophobic effect, destabilizing solvent–protein interactions and stabilizing protein–protein and protein–graphite interactions. Finally, we show how careful consideration of these underlying interactions can be applied to rationally modify the nanostructure morphology.}, journal={JOURNAL OF PHYSICAL CHEMISTRY B}, author={Zorman, Marlo and Phillips, Christian and Shi, Chenyang and Zhang, Shuai and De Yoreo, James and Pfaendtner, Jim}, year={2024}, month={Feb} }
 @article{shi_zorman_zhao_salmeron_pfaendtner_liu_zhang_de yoreo_2024, title={Two-dimensional silk}, volume={10}, ISSN={["2375-2548"]}, DOI={10.1126/sciadv.ado4142}, abstractNote={Despite the promise of silk-based devices, the inherent disorder of native silk limits performance. Here, we report highly ordered two-dimensional silk fibroin (SF) films grown epitaxially on van der Waals (vdW) substrates. Using atomic force microscopy, nano–Fourier transform infrared spectroscopy, and molecular dynamics, we show that the films consist of lamellae of SF molecules that exhibit the same secondary structure as the nanocrystallites of native silk. Increasing the SF concentration results in multilayers that grow either by direct assembly of SF molecules into the lamellae or, at high concentrations, along a two-step pathway beginning with a disordered monolayer that then crystallizes. Scanning Kelvin probe measurements show that these films substantially alter the surface potential; thus, they provide a platform for silk-based electronics on vdW solids.}, number={38}, journal={SCIENCE ADVANCES}, author={Shi, Chenyang and Zorman, Marlo and Zhao, Xiao and Salmeron, Miquel B. and Pfaendtner, Jim and Liu, Xiang Yang and Zhang, Shuai and De Yoreo, James J.}, year={2024}, month={Sep} }
 @article{intan_pfaendtner_2023, title={Role of Surface Features on the Initial Dissolution of CH<sub>3</sub>NH<sub>3</sub>PbI<sub>3</sub> Perovskite in Liquid Water: An Ab Initio Molecular Dynamics Study}, volume={17}, ISSN={["1936-086X"]}, DOI={10.1021/acsnano.3c04601}, abstractNote={The degradation of CH3NH3PbI3 (MAPbI3) hybrid organic inorganic perovskite (HOIP) by water has been the major issue hampering its use in commercial perovskites solar cells (PSCs), as MAPbI3 HOIP has been known to easily degrade in the presence of water. Even though there have been numerous studies investigating this phenomenon, there is still no consensus on the mechanisms of the initial stages of dissolution. Here, we attempt to consolidate differing mechanistic interpretations previously reported in the literature through the use of the first-principles constrained ab initio molecular dynamics (AIMD) to study both the energetics and mechanisms that accompany the degradation of MAPbI3 HOIP in liquid water. By comparing the dissolution free energy barrier between surface species of different surficial types, we find that the dominant dissolution mechanisms of surface species vary widely based on the specific surface features. The high sensitivity of the dissolution mechanism to surface features has contributed to the many dissolution mechanisms proposed in the literature. In contrast, the dissolution free energy barriers are mainly determined by the dissolving species rather than the type of surfaces, and the type of surfaces the ions are dissolving from is inconsequential toward the dissolution free energy barrier. However, the presence of surface defects such as vacancy sites is found to significantly lower the dissolution free energy barriers. Based on the estimated dissolution free energy barriers, we propose that the dissolution of MAPbI3 HOIP in liquid water originates from surface defect sites that propagate laterally along the surface layer of the MAPbI3 HOIP crystal.}, number={22}, journal={ACS NANO}, author={Intan, Nadia N. and Pfaendtner, Jim}, year={2023}, month={Nov}, pages={22371–22387} }
 @article{summers_kraft_alamdari_pfaendtner_kaar_2020, title={Enhanced Activity and Stability of Acidothermus cellulolyticus Endoglucanase 1 in Ionic Liquids via Engineering Active Site Residues and Non-Native Disulfide Bridges}, volume={8}, url={http://dx.doi.org/10.1021/acssuschemeng.0c03242}, DOI={10.1021/acssuschemeng.0c03242}, abstractNote={We report the rational mutagenesis and engineering of endoglucanase 1 (E1) from Acidothermus cellulolyticus, an industrially relevant cellulase, for improved biomass conversion in ionic liquids. Th...}, number={30}, journal={ACS Sustainable Chemistry & Engineering}, publisher={American Chemical Society (ACS)}, author={Summers, Samantha and Kraft, Casey and Alamdari, Sarah and Pfaendtner, Jim and Kaar, Joel L.}, year={2020}, month={Aug}, pages={11299–11307} }
 @article{beckner_mao_pfaendtner_2018, title={Statistical models are able to predict ionic liquid viscosity across a wide range of chemical functionalities and experimental conditions}, volume={3}, url={http://dx.doi.org/10.1039/c7me00094d}, DOI={10.1039/c7me00094d}, abstractNote={Herein we present a method of developing predictive models of viscosity for ionic liquids (ILs) using publicly available data in the ILThermo database and the open-source software toolkits PyChem, RDKit, and SciKit-Learn.}, number={1}, journal={Molecular Systems Design & Engineering}, publisher={Royal Society of Chemistry (RSC)}, author={Beckner, Wesley and Mao, Coco M. and Pfaendtner, Jim}, year={2018}, pages={253–263} }
 @article{tung_pfaendtner_2016, title={Kinetics and mechanism of ionic-liquid induced protein unfolding: application to the model protein HP35}, volume={1}, url={http://dx.doi.org/10.1039/c6me00047a}, DOI={10.1039/c6me00047a}, abstractNote={We demonstrate an approach to quantify protein unfolding times using molecular simulation in a greatly accelerated manner compared to standard MD simulations, showing up to 400 fold speed increases.}, number={4}, journal={Molecular Systems Design & Engineering}, publisher={Royal Society of Chemistry (RSC)}, author={Tung, Hsin-Ju and Pfaendtner, Jim}, year={2016}, pages={382–390} }