(54d) Exploring Gas Diffusion in Carbon Monoxide Dehydrogenase/Acetyl-CoA Synthase (CODH/ACS) Enzyme Complex Using Molecular Simulations.

The carbon monoxide dehydrogenase (CODH) and acetyl-CoA synthase (ACS) enzymatic complex catalyzes the (reversible) electrochemical conversion of CO₂ to CO and the subsequent condensation of CO with a methyl intermediate and coenzyme A to form acetyl coenzyme A. CO₂ reduction happens at the CODH C-cluster, and the CO product is transported and consumed at the ACS A-cluster. The bifunctionality of the complex is facilitated by a 140 Ã…-long gas channel for the transport of CO between the C- and A-clusters.

CODH and the CODH/ACS are central for atmospheric carbon monoxide oxidation and supporting microbial life. These enzymes are also the focus of recent biotechnological applications because of their potential replacement of two energy-intensive industrial processes: 1) the water–gas shift reaction, a widely used industrial process for H₂ or CO production, and 2) the Monsanto process used to produce acetic acid from methanol and CO. However, the effective and widespread use of CODH and CODH/ACS for industrial fields is limited by their poor activity under aerobic conditions. One strategy to design O₂-tolerant complexes is to prevent O₂ from entering the enzyme matrix.

In this work, we use atomistic free energy simulations to explore the gas diffusion through the CODH/ACS complex from M. thermoacetica and other design variants that favor uptake of CO₂ and O₂. We also explore how the transport mechanism is affected by conformational changes in the subunits of the enzyme caused due to transformation of cavities and gating mechanism of residues.

Research Interests:

“Peptoids” as a viable biomaterial in food packaging industry.

Antifreeze proteins (AFPs) stand as a paradigm-shifting innovation, that prevent freezing in organisms living in sub-zero environments by inhibiting ice crystallization. AFPs, such as Type I AFP from winter flounder and Type III AFP from ocean pout, have been instrumental in preventing ice crystallization in biological and industrial settings. This unique function has profound implications in cryopreservation, organ transplant technology, and notably in the food industry, where AFPs play a pivotal role in enhancing product longevity and quality.

Peptoids are synthetically engineered polymers, that could mimic natural AFPs with enhanced flexibility. The fundamental distinction between peptoids and peptides, while structurally similar, differ in the placement of their side chains. In peptides, side chains are attached to the alpha carbon atoms, whereas in peptoids, they are bonded to the nitrogen atoms of peptide backbone. Peptoids could be customized with targeted functional properties, to increase stability against enzymatic degradation, higher resilience under various physical conditions, and a reduced risk of immune responses, making them more suitable for industrial applications.

The research will address critical scientific questions: How do structural variations in peptoids influence their binding efficiency and antifreeze activity compared to natural AFPs? What thermodynamic and kinetic parameters are crucial in determining the antifreeze efficiency of peptoids? How can molecular dynamics simulations contribute to the design of optimized peptoid AFPs for industrial applications, particularly in food packaging?

Circular economy: Conversion of biomass-plastic waste to biochar-based adsorbents.

The crisis of plastic waste, particularly the accumulation of microplastics in the environment, presents a critical challenge for sustainable development. Addressing this issue requires innovative solutions that not only decompose plastic waste but also repurpose it into beneficial materials. Artificial metalloenzymes (ArMs) offer a targeted approach to catalyze the degradation of resistant plastic polymers, transforming them into value-added products such as biochar. Biochar, derived from the carbonization of organic matter, is recognized for its adsorptive properties, and is proposed mechanism to sequester pollutants.

Natural metalloenzymes like laccase and manganese peroxidase catalyze essential reactions in biological systems, including the degradation of complex molecules. Mimicking natural enzymes, artificial metalloenzymes can be engineered to target the sturdy chemical bonds in plastics such as polyethylene terephthalate (PET), high-density polyethylene (HDPE), and polystyrene (PS). Advanced molecular simulation techniques coupled with rational design and directed evolution can finely tune the active sites of metalloenzymes for specific substrate interaction, enhance catalytic rates, and provide stability against harsh industrial conditions.

The research aims to: Design artificial metalloenzymes with enhanced specificity for breaking down multiple types of plastics, focusing on the creation of intermediates destined for biochar conversion. Explore metabolic engineering of microorganisms to host these ArMs, evaluate the life-cycle of the enzymatic byproducts, and upscale the entire process for industrial use. Successful implementation would represent a dual achievement: mitigating plastic pollution and harnessing the resulting biochar for environmental adsorption applications, thereby fostering a circular economy in waste management.

PFAS-mediated dysregulation of biomolecular condensates.

The pervasive presence of per- and polyfluoroalkyl substances (PFAS) in the environment, coupled with their long biological half-life, has emerged as a concern for public health. PFAS compounds like PFOA and PFOS, notorious for their toxicity, exposure to it is linked to a multitude of health risks, and there is a critical need to understand their interaction with cellular components at a molecular level. This research focuses on the impact of PFAS on biomolecular condensates, which are crucial for various cellular processes, including RNA metabolism, signal transduction, and the stress response.

Biomolecular condensates, formed via liquid-liquid phase separation, are highly dynamic and sensitive to changes in their microenvironment. The physicochemical properties of PFAS, such as their hydrophobicity and stability, make them potential disruptors of the condensates' structural integrity. PFAS affect biomolecular condensates at the molecular level, this research aims to utilize molecular simulations to bridge the gap between environmental exposure and cellular dysfunction, offering a foundational perspective on the health implications of PFAS. This work has the potential to inform risk assessments, shape regulatory decisions, and inspire the development of therapeutic interventions to counteract the detrimental effects of PFAS on human health.

Teaching Interests:

The beauty of academic life is that it gives an opportunity to learn, teach, and work with young, bright, and dynamic students, who are the future of our society. Through the influences of the great teachers, I am at this stage to pursue academic life as a part of devoted teaching and research to serve our society. In the following, I describe in detail experiences, teaching philosophy, and plan for teaching.

Teaching experience: I have had a privilege of being TA for the computational biotechnology practical courses of MSc students at University of Galway, Ireland and RWTH Aachen University, Germany. In addition, I co-mentored theses of BSc, MSc students, and students.

Teaching Philosophy: In my opinion, the most important aspect of teaching is that we learn, teach, work, and develop together for the welfare and service of our society. I believe that we can learn best by "doing". The fundamental aspect of teaching is igniting the mind of students with the curiosity and skills necessary to develop questions as well as guide them one-step further to motivate, promote and develop skills and scientific processes necessary to investigate the answers to those questions. To facilitate this, I will keep my classes interactive and open for discussion. Besides, I will take the opportunity to discuss teaching, learning, training, and research with students, friends, colleagues, senior professors, and experts for the betterment of my service to the institute and society.

Teaching Plan: I am interested in teaching the core and professional courses of Biochemical Engineering. In the core courses, I am in the teaching of Protein thermodynamics, Statistical mechanics, Chemical kinetics, and Chemical reaction Engineering. In the professional courses, I would like to teach Bioinformatics, Structural Biology, and Biophysics. Besides, I have the interest to design courses, e.g., Bioeconomy, Protein Engineering.