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Biochemistry
Skills for
Drug Discovery
A Biochemical Society position statement | February 2014

Drug skills position statement
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In this paper we seek to identify and discuss some of the most
significant topics in modern drug discovery where young biochemists
can have a major impact
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Introduction
Modern drug design and development is a complex process that brings together numerous
chemical, biological and clinical disciplines
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These range from early involvement in the identification
and validation of potential molecular targets for new drug projects, to key roles in assay
design, troubleshooting and implementation throughout the screening and optimization
stages of both traditional small molecules and biopharmaceutical products
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At a later stage
in new drug research, biochemical assays are needed to evaluate disease models and to
drive biomarker analysis in translational medicine and clinical research
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At a more biophysical
level, biochemists may contribute significantly to computational chemistry and structural
analysis, such as crystallography or other methods employed to demonstrate drug-binding
modes and to predict potential modifications and improvements of lead compounds
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New drug opportunities
provided by various nucleic acid-based disease interventions, including gene replacement,
use of micro RNA gene silencing or exploitation of other novel methods for controlling
gene expression may draw more biochemistry graduates into pharmaceutical and drug
discovery careers
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Key knowledge, skills and
capabilities for biochemists
Any list of key knowledge, skills and capabilities is inevitably dynamic
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Biochemical basics
These should be central to all undergraduate courses in biochemistry
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This
can leave newer generations of students struggling with some basic concepts
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Analytical skills
Accurate identification and precise measurements of biochemical entities supports many
aspects of the life sciences, none more so than in drug design
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g
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The last of these, imaging and high-throughput microscopy, is an area of growth and rapid
change that offers novel approaches to drug screening and creates high content assay
formats that the industry is adopting so researchers with specific training in these areas
will be needed
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Assay design and statistics
Young scientists need to be able to design their own experimental protocols with a clear
understanding of how to ensure they generate data that are fit-for-purpose
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g
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A good grounding in assay design

Drug skills position statement
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Our graduates should be conversant with data analysis and aware of the importance
of understanding data distribution and the differences and relevance of arithmetic and
geometric means and how to use these calculations appropriately
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The relationships and importance of different ways of quantifying
binding interactions and their affinities from concentration/effect curves, kinetic rate
constants or thermodynamic measurements can each have a role in characterizing drug–
target interactions when the biochemists studying these parameters are well informed
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There are many underlying elementary principles that are common to these two protein
types and students should appreciate their similarities and differences
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The nature and impact of rate constants (particularly dissociation
rates) on assay design, the data produced and its interpretation should all be represented in
the core knowledge set
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Frequently, faults or imbalances in a signalling process drive disease
pathology
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A sound knowledge of the messengers and sometimes complex
pathways and networks involved will continue to be one of the most important topics for
young scientists to grasp as they move into careers in medical and drug research
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Molecular pathology
Understanding the biochemical basis of disease pathology is one of drug discovery’s main
challenges and we might anticipate thorough education and training in the techniques and
principles that can be employed will be a cornerstone of drug discovery skills training
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Pharmacokinetics and drug metabolism
Evaluation of drug metabolism requires biochemists who are conversant with some of
the most elementary skills in isolating and identifying reaction products and blood-borne
metabolites
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This requires considerable
skill in designing suitable assays and interpreting their output, but offers greater
opportunity for small drug discovery units to provide predictive data about the likely fate of
their products in vivo without recourse to animal experimentation
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At the early stages of discovery, the
cytotoxicity of potential therapeutics can be assessed against a range of cell types,
including hepatocyte toxicity and phopsholipidosis potential or monitoring interactions
with hERG channels
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Bioinformatics, ’X-omics‘ and ’Big data’
Activities such as the human genome project, genome-wide association studies and
informatics have identified very many potential biochemical targets for new drugs;
elucidating which of these offer authentic potential is an emerging modern challenge
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In particular, it seems timely for graduates to be able to understand the
outlines of analytical approaches and the types of visualization available for such analysis
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proteomic experimentation or from automated high-throughput and high-content assays
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Systems biology
Most of the diseases for which new treatments are now sought are multi-factorial
and medication is often with drug combinations
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The net behaviour of these systems is too complex
to be understood intuitively, arising as it does from non-linear interactions between
multiple components
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Models can
also function to integrate diverse experimental information, including high-throughput
data, enzyme kinetics, inhibition constants and pharmacokinetic data, as well as cellbased assays, animal experimentation and biomarker measurements
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It may also need to take into account the spatio-temporal
concentrations and compartmentalization of the relevant components
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Systems biology
requires a team approach where skills of practical and theoretical biochemistry combine
in creating and testing of models
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Structural biochemistry, crystallography and other physical techniques to
derive structural information, including molecular modelling
Advances in high-throughput crystallography and other biophysical techniques for the
determination of biomolecular 3D structures has enabled structure-based drug design
to emerge from an area of great potential in the 1980s to its present role as a powerful
contributor to lead compound discovery and optimization
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Experimental and
modelled protein structures are now routinely used alongside computational docking in
virtual screening of chemical libraries to accelerate the search for new drug molecules
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Bioinformatics, data mining, systems biology and structural biology are all dependent
on considerable mathematical ability and advanced computing skills
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There is little doubt, biochemistry underpins in silico approaches to drug
discovery and development that are likely to contribute significantly to the therapeutic
portfolio of our pharma industry over the coming years
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Antibody-based
therapies in particular have seen huge growth in the last decade and some predictions
suggest they will soon dominate drug sales
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This would include a
working knowledge of monoclonal antibodies and how they are produced
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Antibody engineering is of particular importance in creating effective, safe biologic
therapies so it may be envisaged that questions of humanization and other forms of protein
modification to address pharmacokinetics, immunogenicity and stability should become
widely understood among biochemists
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Practices in outsourcing
The use of external collaborations and contract research organizations has grown within
the industry; in some cases to the extent that models similar to many start-up companies
where all research activities are outsourced now operate within major pharmaceutical firms
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Drug skills position statement
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This may serve to allow
students to make well-informed career decisions and ensure graduates have more rapid
impact when they move into drug discovery roles
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Rising costs in drug discovery, coupled with high attrition rates throughout the pipeline,
particularly during clinical trials, have been a major cause for concern within the drug
industry in recent years
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This will require excellent knowledge transfer between scientists with industrial experience
and young researchers, such that lessons that we have already learned are passed on and
the science of drug discovery can develop and grow to the benefit of patients
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Although we may
promote specific business aspects, our graduates need to appreciate they are not universal,
however, the underlying principles can be widely applied
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Drug skills position statement
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Indeed, there is probably more than enough material relevant to drug discovery
to offer entire degree courses concentrating on this subject
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Let us not lose sight of the fact that a strong basic training in the
fundamental elements of our subject is the essential foundation on which to build this
knowledge and expertise for drug discovery
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Biophysical
techniques in particular have potential for much greater impact on the design and
optimization of new chemical entities
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Interaction and close
cooperation with those working in different subject areas is vital in order to facilitate
effective meaningful exchange of data and information so that everyone may contribute
to intelligent decision-making within the drug design and development process
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The
needs of the pharmaceutical industry, large pharma, smaller R&D companies, the biotech
sector, start-up companies and contract research organizations must be met by the training
of young scientists and should enable graduates to function in all of these environments
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This might include
gene therapy, tissue repair and regeneration and include stem cell technology and novel
forms of drug delivery, as well as the traditional approaches
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Finally, it is crucial that the pharmaceutical industry, in all of its guises, endorse and embrace
these initiatives and recognize their value
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This document was created in February 2014 and will be reviewed regularly
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Drug skills position statement
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We achieve our mission though our publications and journals, scientific meetings,
educational activities, policy work, awards, and grants to scientists and students
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org
Policy Team
Tel: +44 (0)20 7685 2453
Email: policy@biochemistry
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org

www
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org

@BiochemSoc



Biochemical Society

Registered charity No
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