This document discusses issues with commonly used methods in molecular design and data analysis, including ligand efficiency metrics (LEMs). It argues that LEMs make unfounded assumptions about relationships between activity and risk factors. Instead, residuals from modeling activity data directly should be used to quantify how much activity exceeds trends, as they are invariant to choices like standard concentration and treat all risk factors consistently. The document advocates understanding data properties before analysis and avoiding practices like arbitrarily binning data that can distort correlations.
Aspects of pharmaceutical molecular designPeter Kenny
Presented at ResearResearch Center for Molecular Medicine of the Austrian Academy of Sciencesch Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM) in July 2014 to a non-chemist audience. Not sure how it worked but it was an enjoyable visit and nobody fell asleep in the talk.
This document discusses issues with commonly used methods in molecular design and data analysis, including ligand efficiency metrics (LEMs). It argues that LEMs make unfounded assumptions about relationships between activity and risk factors. Instead, residuals from modeling activity data directly should be used to quantify how much activity exceeds trends, as they are invariant to choices like standard concentration and treat all risk factors consistently. The document advocates understanding data properties before analysis and avoiding practices like arbitrarily binning data that can distort correlations.
Aspects of pharmaceutical molecular designPeter Kenny
Presented at ResearResearch Center for Molecular Medicine of the Austrian Academy of Sciencesch Center for Molecular Medicine of the Austrian Academy of Sciences (CeMM) in July 2014 to a non-chemist audience. Not sure how it worked but it was an enjoyable visit and nobody fell asleep in the talk.
Aspects of pharmaceutical molecular design (Belgrade version)Peter Kenny
Peter W Kenny discusses various aspects of pharmaceutical molecular design. Some key challenges in drug discovery include exploiting weakly linked disease targets, predicting toxicity, and measuring free drug concentrations in vivo. Molecular design aims to control compound behavior through molecular properties. Both hypothesis-driven and prediction-driven approaches are used, along with sampling chemical space. Target engagement potential is proposed as a basis for design, with objectives of low target binding, high anti-target binding, and control of free drug concentrations. Property-based design searches for an optimal "sweet spot" of affinity and ADMET properties. Hypothesis-driven design uses structure-activity relationships as an efficient framework, while prediction-driven design builds predictive models.
This document discusses molecular design for drug discovery. It outlines how molecular design can be used to control compound behavior through manipulation of molecular properties. Hypothesis-driven and prediction-driven approaches to molecular design are discussed. Relationship between structures, such as bioisosterism, are important for analyzing biological activity and physicochemical properties. Library design for screening is also covered, focusing on diversity, coverage, and neighborhood sampling of chemical space.
Aspects of pharmaceutical molecular design (Fidelta version)Peter Kenny
This document discusses various aspects of pharmaceutical molecular design. It touches on three key points:
1) Pharmaceutical molecular design aims to control compound behavior through manipulation of molecular properties in a hypothesis-driven or prediction-driven manner.
2) Hypothesis-driven design frameworks help efficiently assemble structure-activity relationships to better understand molecules and ask insightful questions.
3) Prediction-driven design assumes predictive models can be built with sufficient accuracy, though issues like non-uniform sampling of chemical space and overfitting remain challenges.
Hydrogen bonding and molecular design (BrazMedChem 2010)Peter Kenny
This document discusses hydrogen bonding and its importance in molecular design for drug discovery. It provides examples of how measuring and modeling hydrogen bond strength can help predict properties like solubility, potency and permeability. Electrostatic potential is shown to correlate with experimental hydrogen bond acidities and basicities. The document advocates considering hydrogen bonding explicitly in molecular properties and modeling, rather than only focusing on parameters like lipophilicity. It also questions some common assumptions and provides references for further reading on quantifying hydrogen bonding.
Design of compound libraries for fragment screening (Feb 2012 version)Peter Kenny
Slimmed down fragment screening library talk presented at University of Adelaide (Dec 2011) and Pharmaxis (Feb 2012). Includes dingo and Maria Sharapova (losing finalist at 2012 Australian Open). The photo for the title slide is of a range finder from the Admiral Graf Spee and was taken in Montevideo.
Design of fragment screening libraries (IQPC 2008)Peter Kenny
This document discusses the design of fragment screening libraries for fragment-based drug discovery. It describes how fragment hits have high ligand efficiency due to their low molecular weight. The document outlines criteria for selecting fragments, including molecular complexity, solubility, and availability of chemical neighbors. It presents details on the design of the GFSL05 20,000 compound screening library from AstraZeneca, including controlling molecular properties like size, lipophilicity, and structural diversity. Literature on fragment-based screening and library design is also cited.
El documento describe el atletismo, que incluye carreras, saltos y lanzamientos. Las carreras incluyen carreras de velocidad, obstáculos, fondo, medio fondo y relevos. Los saltos incluyen salto de altura, triple salto y salto con pértiga y de longitud. Los lanzamientos incluyen lanzamiento de peso, martillo, disco y jabalina. También se menciona el material utilizado en cada prueba.
2. QUÈ SÓN LES QUALITATS FÍSIQUES
BÀSIQUES?
Conjunt de propietats de l'organisme que li
permeten realitzar tota mena de moviments
(jugar, caminar, nedar...)
8. Planteja't les preguntes següents:
1.Has hagut d'aturar mai de jugar perquè estaves
molt cansat?
Això es perquè et faltava la qualitat física que et
permet resistir esforços llargs i que s'anomena ....
RESISTÈNCIA
9. 2. T'agradaria saltar més lluny en un salt de llargada?
Per aconseguir-ho necessitaras una qualitat física
anomenada...
FORÇA
10. 3. Oi que en les classes d'educació física has
participat en algunes curses de relleus?
Mentre corries utilitzaves una qualitat física que ens
permet desplaçar-nos rápidament: la ...
VELOCITAT
11. 4. Quan estàs dret o assegut a terra pots tocar-te la
punta dels pues amb les mans sense doblegar els
genolls?
Per fer-ho necessites una qualitat física que et
permet arribar a realitzar moviments molt amplis: la ...
FLEXIBILITAT
