Workshop 1: Amsterdam Density Functional ADF2020.

Predicting and Understanding Molecular Properties!

Pr. Lotfi Belkhiri (UFM Constantine1)

Abstract

Computational modeling is based on recognizing the relationship between a structure and its molecular properties. The increasing availability of fast computers and a wide variety of suitable chemical drawing and modeling programs at relatively low cost now allows access to computational chemistry from an advanced undergraduate level onwards.

This workshop aims to provide molecular modeling and computational techniques dealing with physicochemical and bioactivity properties as well as the reactivity using state-of-the-art quantum chemistry i.e. the powerful Density Functional Theory DFT.

Outline

I. Introduction and overview of the ADF Suite

a) Presentation of Graphical User Interface GUI of ADF software.

b) Getting started: building molecules, basic calculations, eg. geometry optimization of ethanol…

c) Advanced methods for including environmental effects e.g. solvation with COSMO (Continuum Screening Model) method.

d) Easy exercises from MOs, HOMO-LUMO, spin density... etc) with many spectroscopic properties: vibrational frequencies IR of ethane and UV-Vis spectrum of ethene

e) Many bonding analysis tools (EDA, ETS-NOCV, QTAIM, NCI, Fukui, IQA) The ADF comes with various analysis tools offering a detailed insight into the nature of individual chemical bonds and properties like charges, electron densities, and potentials. We will check out our analysis tutorials with examples for EDA, with NOCV, QTAIM, Fukui functions.

g) Multiple molecules, conformers, multiple methods: The ADF-GUI can handle multiple molecules and can generate conformers with multiple methods. The refinement of conformers using different theoretical methods, and the calculation of properties like spectra (UV/Vis, IR, NMR, and others) weighted throughout spectra of the individual conformers.

II. Application to pharma and life sciences

The chemical bonding analysis tools and many spectroscopic properties in ADF give valuable insight into ligand binding, conformations, and absolute configuration. Force fields, semi-empirical methods, and DFT all available with the graphical interface (GUI), and scripting allows for easy workflows. The solvation module COSMO can predict solubilities and partition coefficients from first principles for active pharmaceutical ingredients for various solvent combinations, including excipients.

a) Vibrational Circular Dichroism (VCD) analysis tools: This tip will show how to calculate and analyze the VCD spectrum of a small molecule (Oxirane) using ADF and VCDtools.

This predictive useful tool for bioactive molecules and R/S chiral separation will focus on:

b) DFTB: 1000s of atoms, DFTB3 parameters for most pharmaceutical compounds

c) ReaxFF: with reactive force fields for biochemistry

d) Various free energy methods and MD analysis via the PLUMED library

e) COSMO-RS & COSMO-SAC: solubilities, logP, pKa, VLE, etc. based on DFT + thermodynamics.