Andrew Paluch

• Doctor of Philosophy
• Miami University

Aging is a natural process that is also influenced by some factors like the food someone eats, lifestyle decisions, and impacts on general health. Despite the recognized role of nutrition in modulating the molecular and cellular mechanisms underlying aging, there is a lack of comprehensive exploration into potential interventions that can effective...

Aging is a natural process that is also influenced by some factors like food someone eats, lifestyle decisions, and impacts on general health. Despite the recognized role of nutrition in modulating the molecular and cellular mechanisms underlying aging, there is a lack of comprehensive exploration into potential interventions that can effectively m...

PERSPECTIVE Miroslava Nedyalkova, Marco Lattuada et al. Progress and future of the computational design of antimicrobial peptides (AMPs): bio-inspired functional molecules Progress and future of the computational design of antimicrobial peptides (AMPs): bio-inspired functional molecules

PERSPECTIVE Miroslava Nedyalkova, Marco Lattuada et al. Progress and future of the computational design of antimicrobial peptides (AMPs): bio-inspired functional molecules

The effectiveness of antibiotics is greatly enhanced by their ability to target invasive organisms involved in the ancient evolutionary battle between hosts and pathogens. Conventional antibiotics no longer offer adequate protection due to the evolution of strategies to evade them. As a result, efforts are needed to design novel replacement antibio...

Human thymidylate synthase (hTS) is a validated drug target for chemotherapy. A virtual screening experiment was used to prioritize a list of compounds from African Natural Products Databases docked against the orthosteric binding pocket of hTS. Consensus scores of binding affinities from ensemble-based virtual screening, hydrated docking and MM-PB...

In general, for an organic compound a plot of the log vapor pressure versus inverse temperature is linear over a wide temperature range. This however can lead to a point of confusion in an undergraduate thermodynamics course. This linear behavior is typically explained using the Clausius/Clapeyron equation. That is, starting with the Clapeyron equa...

In general, for an organic compound a plot of the log vapor pressure versus inverse temperature is linear over a wide temperature range. This however can lead to a point of confusion in an undergraduate thermodynamics course. This linear behavior is typically explained using the Clausius/Clapeyron equation. That is, starting with the Clapeyron equa...

Tools to predict vapor–liquid phase equilibria are indispensable for the conceptualization and design of separation processes. Modified separation of cohesive energy density (MOSCED) is a solubility-parameter-based method parameterized to make accurate predictions of the limiting activity coefficient. As a solubility-parameter-based method, MOSCED...

For a binary mixture without azeotrope, its boiling temperature at quasi-infinite dilution TbQID< Tb,H (the higher boiling temperature of the two components), and TbQID> Tb,L (the lower boiling temperature of the two components). For a binary mixture with minimum boiling azeotrope,TbQID < Tb,L at the neighbourhood of the lower-boiling-temperature c...

A drug repositioning computational approach was carried to search inhibitors for human thymidylate synthase. An ensemble-based virtual screening of FDA-approved drugs showed the drugs Imatinib, Lumacaftor and Naldemedine to be likely candidates for repurposing. The role of water in the drug-receptor interactions was revealed by the application of a...

Blind predictions of octanol/water partition coefficients and pKa at 298.15 K for 22 drug-like compounds were made for the SAMPL7 challenge. Octanol/water partition coefficients were predicted from solvation free energies computed using electronic structure calculations with the SM12, SM8 and SMD solvation models. Within these calculations we compa...

A drug repositioning computational approach was carried to search inhibitors for human thymidylate synthase. An ensemble-based virtual screening of FDA-approved drugs showed the drugs Imatinib, Lumacaftor and Naldemedine to be likely candidates for repurposing. The role of water in the drug-receptor interactions was revealed by the application of a...

Methods to predict the equilibrium solubility of nonelectrolyte solids are indispensable for early-stage process development, design, and feasibility studies. Conventional analytic methods typically require reference data to regress parameters, which may not be available or limited for novel systems. Molecular simulation is a promising alternative,...

Linamarin has been reported to have anticancer activities; however, its extraction and isolation using different solvents yield a low amount. Therefore, understanding the physical properties, such as solvents’ solubility, membrane permeability and lipophilicity and how they are associated with different solvents, is a paramount topic for discussion...

COVID-19, a disease caused by the SARS-CoV-2 virus, is responsible for a pandemic since March 2020 and it has no cure. Therefore, herein, different theoretical methods were used to obtain potential candidates from herbal compounds to inhibit the SARS-CoV-2 main protease (Mpro). Initially, the 16 best-scored compounds were selected from a library co...

Blind predictions of octanol/water partition coefficients at 298.15 K for 22 drug-like compounds were made for the SAMPL7 challenge. The octanol/water partition coefficients were predicted using solvation free energies computed using molecular dynamics simulations, wherein we considered the use of both pure and water-saturated 1-octanol to model th...

Understanding the solubility of flavonoids is of relevance in view of the broad application such as antioxidant and antitumor agents. The solubility of flavonoid rutin has been experimentally investigated in a homologous series of alcohols, acetone, n-heptane and water solvents. In this work theoretical evaluation of Gibbs free energy of solvation...

Blind predictions of octanol/water partition coefficients at 298 K for 22 drug-like compounds were made for the SAMPL7 challenge. The octanol/water partition coefficients were predicted using solvation free energies computed using molecular dynamics simulations, wherein we considered the use of both pure and water-saturated 1-octanol to model the o...

Herein, molecular modeling techniques were used with the main goal to obtain candidates from a drug database as potential targets to be used against SARS-CoV-2. This novel coronavirus, responsible by the COVID-19 outbreak since the end of 2019, became a challenge since there is not vaccine for this disease. The first step in this investigation was...

The SMx (x = 12, 8, or D) universal solvent models are implicit solvent models which using electronic structure calculations can compute solvation free energies at 298.15 K. While solvation free energy is an important thermophysical property, within the thermodynamic modeling of phase equilibrium, limiting (or infinite dilution) activity coefficien...

Blind predictions of octanol/water partition coefficients at 298 K for 11 kinase inhibitor fragment like compounds were made for the SAMPL6 challenge. We used the conventional, “untrained”, free energy based approach wherein the octanol/water partition coefficient was computed directly as the difference in solvation free energy in water and 1-octan...

The SM x ( x = 12, 8, or D) universal solvent models are implicit solvent models which using electronic structure calculations can compute solvation free energies at 298.15 K. While solvation free energy is an important thermophysical property, within the thermodynamic modeling of phase equilibrium, limiting (or infinite dilution) activity coeffici...

MOSCED (modified separation of cohesive energy density) is a solubility parameter method that offers an improved treatment of association interactions. Solubility parameter methods are well known for their ability to both make quantitative predictions and offer a qualitative description of the underlying molecular-level driving forces, lending them...

Simple expressions are presented to determine if a binary system will exhibit a minimum or maximum boiling azeotrope using conventional free energy calculations using molecular simulation or electronic structure calculations in a continuum solvent. The expressions compare the solvation free energy of each component in the other at infinite dilution...

Solubility parameter based methods have long been valuable design tools due to their ability to make both quantitative predictions and to shed insight into the underlying intermolecular interactions. The use of MOSCED (modified separation of cohesive energy density) is particularly attractive due to its advanced treatment of association interaction...

MOSCED (Modified Separation of Cohesive Energy Density) is a powerful analytic tool for predicting phase behavior. Additionally, as a solubility parameter based method, it can be used to gain insight into the underlying molecular-level interactions for intuitive solvent selection and formulation. The major advancement of MOSCED over other solubilit...

As a result of their high tuneability and low volatility, room temperature ionic liquids have been proposed as replacement solvents in a wide range of industrial applications. They are particularly well-suited for use as an entrainer (or solvent) in extractive distillation processes to separate close boiling and azeotropic mixtures. The limiting se...

Fixed-charge force fields are a common choice for modelling solvents, many of which have been optimised around pure-component property predictions. Their use for modelling solvent mixtures, however, is questionable as the charge distribution of a molecule in the pure component and infinite dilution limits are expected to be different. Due to the sm...

The modified separation of cohesive energy density (MOSCED) is a powerful tool for early stage process conceptualization and design. It is capable of making quantitative phase-equilibrium calculations, and more importantly may be used to qualitatively understand the underlying molecular level details of a system for intuitive process design. Unfort...

Modified Separation of Cohesive Energy Density (MOSCED) is a solubility parameter-based method to predict limiting activity coefficients. In addition to making quantitative predictions, MOSCED may additionally be used to understand the underlying molecular-level driving forces for intuitive solvent selection and formulation. A major improvement of...

MOSCED (MOdified Separation of Cohesive Energy Density) is an attractive method for modeling phase-equilibria because it both can make quantitative predictions and give insight into the system's underlying molecular-level interactions. While MOSCED predicts satisfactory values of limiting activity coefficients of organics in water, we find that pre...

The MOdified Separation of Cohesive Energy Density (MOSCED) is a solubility parameter based method that can both quantitatively predict limiting activity coefficients and can additionally be used to qualitatively understand the underlying molecular-level interactions for intuitive solvent selection and formulation. However, before predictions may b...

Cassandra is an open source atomistic Monte Carlo software package that is effective in simulating the thermodynamic properties of fluids and solids. The different features and algorithms used in Cassandra are described, along with implementation details and theoretical underpinnings to various methods used. Benchmark and example calculations are s...

Methods to predict the equilibrium solubility of non-electrolyte solids are important for the design of novel separation processes. Here we demonstrate how conventional molecular simulation free energy calculations or electronic structure calculations in a continuum solvent, here SMD or SM8, can be used to predict parameters for the MOdified Separa...

Solubility parameter based methods have long been a valuable tool for solvent formulation and selection. Of these methods, the MOdified Separation of Cohesive Energy Density (MOSCED) has recently been shown to correlate well the equilibrium solubility of multifunctional non-electrolyte solids. However, before it can be applied to a novel solute, a...

The use of room temperature ionic liquids (ILs) as novel solvents in a range of industrial separation processes has received tremendous attention and research. Here, we investigate the potential application of ILs to remove the wastewater contaminants atenolol and atrazine. Specifically, using molecular simulation we predict IL/water partition coef...

Molecular dynamics simulations were employed to both estimate the solubility of the non-electrolyte solids acetanilide, acetaminophen, phenacetin, methylparaben and lidocaine in supercritical carbon dioxide, and to understand the underlying molecular-level driving forces. The solubility calculations involve the estimation of the solute's limiting a...

We present blind predictions using the solubility parameter based method MOSCED submitted for the SAMPL5 challenge on calculating cyclohexane/water distribution coefficients at 298 K. Reference data to parameterize MOSCED was generated with knowledge only of chemical structure by performing solvation free energy calculations using electronic struct...

An efficient method to predict modified separation of cohesive energy density model (MOSCED) parameters for nonelectrolyte solids using electronic structure calculations in SMD and SM8 continuum solvents is proposed and applied to acetanilide, acetaminophen, and phenacetin. The resulting parameters are ultimately used to predict the equilibrium sol...

The Modified Separation of Cohesive Energy Density Model (MOSCED) is an efficient, analytic method to predict infinite dilution activity coefficients over a range of temperatures. Its predictability makes MOSCED an attractive, engineering design tool. However, its use is. limited. When, trying to model a novel compound, reference,data must first be...

During the manufacturing of pharmaceutical compounds, solvent mixtures are commonly used, where the addition of a co-solvent allows for the tuning of the intermolecular interactions present in the system. Here we demonstrate how a similar effect can be accomplished using a room temperature ionic liquid. The pharmaceutical compound acetaminophen is...

Room temperature ionic liquids have been proposed as replacement solvents in a wide range of industrial separation processes. Here, we focus on the use of ionic liquids as solvents for the pharmaceutical compound lidocaine. We show that the solubility of lidocaine in seven common 1-n-butyl-3-methylimidazolium based ionic liquids is greatly enhanced...

Here, our interest is in predicting solubility in general, and we focus particularly on predicting how the solubility of particular solutes is modulated by the solvent environment. Solubility in general is extremely important, both for theoretical reasons -- it provides an important probe of the balance between solute-solute and solute-solvent inte...

Conventional molecular simulation free energy calculations and standard thermodynamic relations are applied to compute the pure liquid fugacity of low volatile liquids and compared to reference Monte Carlo simulations. The method involves the calculation of the residual chemical potential and the molar volume of the liquid at the conditions of inte...

We present a general framework to predict the excess solubility of small molecular solids (such as pharmaceutical solids) in binary solvents via molecular simulation free energy calculations at infinite dilution with conventional molecular models. The present study used molecular dynamics with the General AMBER Force Field to predict the excess sol...

We present an efficient means to estimate the concentration-dependent solution-phase fugacity of soluble nonelectrolyte solids in binary solvents by molecular simulation. The underlying assumption of the proposed method is that the solute does not associate or interact with other solute molecules in solution. Solute–solvent and solvent–solvent inte...

A simple correction to the infinite dilution activity coefficient computed via molecular simulation for a nonelectrolyte solid solute in solution is proposed. The methodology adopts the concept that the activity coefficient may be fundamentally interpreted as a product of a residual and combinatorial term. The residual contribution is assumed to be...

A computational approach is developed to quantitatively study the solvation thermodynamics of amino acid analogues in ionic liquids via molecular simulation. The solvation thermodynamics of amino acid analogues in ionic liquids is important for an understanding of protein-ionic liquid interactions, shedding insight into the structure and solubility...

We present an efficient expanded ensemble molecular dynamics method to calculate the solvation free energy (or residual chemical potential) of small molecules with complex topologies. The methodology is validated by computing the solvation free energy of ibuprofen in water, methanol, and ethanol at 300 K and 1 bar and comparing to reference simulat...

We present an efficient, automated expanded ensemble method to calculate the residual chemical potential or solvation free energy by molecular dynamics simulation. The methodology is validated by computing the residual chemical potential of 13 amino acid analogs in water at 300 K and 1 bar and comparing to reference simulation data. Overall agreeme...

We present a simple method to estimate the solubility of weakly soluble solids in different solvents. The method involves the calculation of the residual chemical potential of a single solute molecule in the solvent of interest using an appropriate atomistic free energy simulation technique. In the present method, an expanded ensemble calculation i...

We present an adaptable method to compute the solubility limit of solids by molecular simulation, which avoids the difficulty of reference state calculations. In this way, the method is highly adaptable to molecules of complex topology. Results are shown for solubility calculations of sodium chloride in water and light alcohols at atmospheric condi...

Despite the development of sophisticated methods to study vapor-liquid equilibrium, the development of methodologies to study solid-liquid equilibrium has received much less attention due to the inherent complexity involved with the calculation of the free energy of solids. In this talk, we will demonstrate a robust method to calculate the solubili...

We present results from a computational study investigating the use of Gibbs ensemble and grand-canonical transition-matrix Monte Carlo (GC-TMMC) methods to determine the liquid−vapor phase coexistence properties of pure molecular fluids of varying degrees of complexity. The molecules used in this study were ethane, n-octane, cyclohexane, 2,5-dimet...