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pradyumn sharma

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Papers by pradyumn sharma

Research paper thumbnail of Evaluating coarse-grained MARTINI force-fields for capturing the ripple phase of lipid membranes

Phospholipids, which are an integral component of cell membranes, exhibit a rich variety of lamel... more Phospholipids, which are an integral component of cell membranes, exhibit a rich variety of lamellar phases modulated by temperature and composition. Molecular dynamics (MD) simulations have greatly enhanced our understanding of phospholipid membranes by capturing experimentally observed phases and phase transitions at molecular resolution. However, the ripple (Pβ′) membrane phase, observed as an intermediate phase below the main gel-to-liquid crystalline transition with some lipids, has been challenging to capture with MD simulations, both at all-atom and coarse-grained resolution. Here, we systematically assess the ability of five coarse-grained MARTINI 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid force-field (FF) variants, parametrized to reproduce the DPPC gel and fluid phases, for their ability to capture the Pβ′ phase. Upon cooling from the fluid phase to below the phase transition temperature with smaller (380-lipid) and larger (> 2200-lipid) MARTINI and all-at...

Research paper thumbnail of Developing a Coarse-Grained Model for Bacterial Cell Walls: Evaluating Mechanical Properties and Free Energy Barriers

Journal of Chemical Theory and Computation

Research paper thumbnail of Small Molecule Interactions with Bacterial Cell Membranes: Assessing Insertion Barriers for all the Membranes using Free Energy Computations

Research paper thumbnail of Developing a Coarse-Grained Model for Bacterial Cell Walls and Evaluating Mechanical Properties and Free Energy Barriers

The bacterial cell envelope of Gram-negative bacteria is a complex biological barrier with multip... more The bacterial cell envelope of Gram-negative bacteria is a complex biological barrier with multiple layers consisting of the inner membrane, periplasm of peptidoglycan and the outer membrane with lipopolysaccharides (LPS). With rising antimicrobial resistance there is increasing interest in understanding interactions of small molecules with the cell membrane to aid in the development of novel drug molecules. Hence suitable representations of the bacterial membrane are required to carry out meaningful molecular dynamics simulations. Given the complexity of the cell envelope, fully atomistic descriptions of the cell membrane with explicit solvent are computationally prohibitive, allowing limited sampling with small system sizes. However coarse-grained (CG) models such as MARTINI allow one to study phenomena at physiologically relevant length and time scales. Although MARTINI models for lipids and the LPS are available in literature, a suitable CG model of peptidoglycan is lacking. In ...

Research paper thumbnail of Assessing Barriers for Antimicrobial Penetration in Complex Asymmetric Bacterial Membranes: A Case Study with Thymol

Research paper thumbnail of Evaluating coarse-grained MARTINI force-fields for capturing the ripple phase of lipid membranes

Phospholipids, which are an integral component of cell membranes, exhibit a rich variety of lamel... more Phospholipids, which are an integral component of cell membranes, exhibit a rich variety of lamellar phases modulated by temperature and composition. Molecular dynamics (MD) simulations have greatly enhanced our understanding of phospholipid membranes by capturing experimentally observed phases and phase transitions at molecular resolution. However, the ripple (Pβ′) membrane phase, observed as an intermediate phase below the main gel-to-liquid crystalline transition with some lipids, has been challenging to capture with MD simulations, both at all-atom and coarse-grained resolution. Here, we systematically assess the ability of five coarse-grained MARTINI 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid force-field (FF) variants, parametrized to reproduce the DPPC gel and fluid phases, for their ability to capture the Pβ′ phase. Upon cooling from the fluid phase to below the phase transition temperature with smaller (380-lipid) and larger (> 2200-lipid) MARTINI and all-at...

Research paper thumbnail of Developing a Coarse-Grained Model for Bacterial Cell Walls: Evaluating Mechanical Properties and Free Energy Barriers

Journal of Chemical Theory and Computation

Research paper thumbnail of Small Molecule Interactions with Bacterial Cell Membranes: Assessing Insertion Barriers for all the Membranes using Free Energy Computations

Research paper thumbnail of Developing a Coarse-Grained Model for Bacterial Cell Walls and Evaluating Mechanical Properties and Free Energy Barriers

The bacterial cell envelope of Gram-negative bacteria is a complex biological barrier with multip... more The bacterial cell envelope of Gram-negative bacteria is a complex biological barrier with multiple layers consisting of the inner membrane, periplasm of peptidoglycan and the outer membrane with lipopolysaccharides (LPS). With rising antimicrobial resistance there is increasing interest in understanding interactions of small molecules with the cell membrane to aid in the development of novel drug molecules. Hence suitable representations of the bacterial membrane are required to carry out meaningful molecular dynamics simulations. Given the complexity of the cell envelope, fully atomistic descriptions of the cell membrane with explicit solvent are computationally prohibitive, allowing limited sampling with small system sizes. However coarse-grained (CG) models such as MARTINI allow one to study phenomena at physiologically relevant length and time scales. Although MARTINI models for lipids and the LPS are available in literature, a suitable CG model of peptidoglycan is lacking. In ...

Research paper thumbnail of Assessing Barriers for Antimicrobial Penetration in Complex Asymmetric Bacterial Membranes: A Case Study with Thymol

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